Cycloheximide enhances maintenance of methamphetamine-induced conditioned place preference.
Accrued evidence demonstrated the necessity of protein synthesis at acquisition, consolidation and expression stages in conditioning/learning tasks, while the underlying mechanisms of the maintenance of memory remained less explored. This study was designed to characterize the maintenance of methamphetamine-induced conditioned place preference, a drug-induced learning and memory. In addition, cycloheximide, a protein synthesis inhibitor, was used to examine the involvement of protein synthesis in the maintenance of such place preference memory. We found that the maintenance of the rapidly-established methamphetamine (2 mg/kg, i.p.) -induced conditioned place preference could be long-lasting and even over fifty days under the present protocol of extinction. Moreover, it was of interest to note the undulating expression of this conditioned place preference throughout the extinction protocol. Most importantly, as the methamphetamine-induced conditioned place preference was acquired and expressed by mice, the saline-pretreated control mice underwent numbers of intermittent extinction across a long-term retention test period, while cycloheximide-pretreated mice exhibited unaltered methamphetamine-induced conditioned place preference throughout the same retention test period. Taken together, we conclude that [1] methamphetamine-induced conditioned place preference could last for a long period of time, and such place preference memory is reluctant to extinguish even animals' repeated exposure to the previous conditioned environment at a drug-free status, and [2] blockade of protein synthesis may enhance the maintenance of the methamphetamine-induced conditioned place preference.


GP-1447, an inhibitor of aldose reductase, prevents the progression of diabetic cataract in rats.
We examined the effects of GP-1447 (3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]-5-methylphenyl acetic acid) on existing cataracts and sorbitol content in the lens in rats with streptozotocin-induced diabetes. GP-1447 is an inhibitor of aldose reductase, which is the first enzyme in the polyol pathway. Cataracts in the central region of the lens were observed in 7 of 14 eyes (50%) by the fifth week after induction of diabetes, and development of mature cataracts was observed in most lenses by the ninth week. In diabetic rats that received GP-1447 treatment beginning in the fifth week after induction of diabetes, progression of cataracts was observed for 1 week after initiation of treatment. Thereafter, the severity of cataracts did not change substantially. Sorbitol levels in the lens peaked during the first week of diabetes, and this increase was maintained during the 9-week observation period. Elevated sorbitol levels in the lenses of diabetic rats gradually declined after GP-1447 treatment was started on the fifth week after induction of diabetes. Cataracts and sorbitol elevation were not observed in the lenses of controls or diabetic rats treated with GP-1447 immediately after induction of diabetes. These results suggest that the polyol pathway plays an important role in both the appearance and progression of cataracts in diabetic rats. Inhibition of aldose reductase could significantly prevent progression of existing cataracts.


Temperature dependence of the emissivity of platinum in the IR.
The accuracy of temperature determination by fitting the spectral irradiance to a Planck curve depends on knowledge of the emissivity at all temperatures and pressures of interest within a spectral region. Here, the emissivity of platinum is measured in the near infrared as a function of temperature. In the wavelength range of study and the temperature range of 650-1100 K, we find the emissivity to be independent of temperature to within experimental error. This result should lead to improved accuracy of temperature measurement by optical pyrometry where platinum is used as a thermal emitter.


Effectiveness of oolong tea and simethicone solution for lens cleansing during colonoscopy: A double-blinded randomized study.
water is an imperfect agent for lens cleansing during endoscopy due to its incompetence to clean hydrophobic dirt, whereas amphiphilic surfactants have the potential to overcome the limitation of water. The trial was aimed to evaluate the cleansing effectiveness of 2 typical surfactants (simethicone solution and oolong tea) for colonoscopic lens. Oolong tea (O-), low concentration simethicone solution (S1-), high concentration simethicone solution (S2-) and distilled water (D-) were used as washing solutions for colonoscopic lens. Study I: The tip of the colonoscope was immersed in lard oil in order to simulate the blur, and photographs were taken toward a standard colonoscopy image in-vitro pre- and post- each cleansing procedure. The blurred areas of each image were quantified and compared. Study II: 395 consecutive patients who were due to colonoscopy examination were enrolled and randomized into O-, S2-, D-group. The volume of washing solution used and cleansing level during the examination procedure, adenoma and polyp detected per colonoscopy, insertion time and withdraw time were analyzed. Study I: There were no differences in 4 groups for the blurred areas on images before lens cleansing. The blurred areas after lens cleansing were significantly smaller in 3 groups (O- 8.47 ± 20.91 vs S1- 13.06 ± 10.71 vs S2- 6.76 ± 8.49 vs D- 38.24 ± 29.69, P < .05) than water. The decline range of blurred areas after lens cleansing in oolong tea, low concentration simethicone solution, high concentration simethicone solution groups were significantly higher than that in distilled water group (O- 87.35 ± 20.81 vs S1- 78.12 ± 19.24 vs S2- 89.57 ± 8.50 vs D- 53.39 ± 28.45, P < .05). Study II: The volume of washing solution used in S2-group was significantly smaller than that in O-group and D-group. The cleansing level of the colonoscopic lens of O-group was significantly superior than that of S2-group and D-group. The in-vitro test showed oolong tea and simethicone solution can effectively cleans the colonoscopic lens. The clinical trial demonstrated that oolong tea instead of water is effective to provide better visualization during colonoscopy.Registration: Chictr.org.cn No: ChiCTR1900025606.


Medical ethics in India.
Medical ethics in the Indian context is closely related to indigenous classical and folk traditions. This article traces the history of Indian conceptions of ethics and medicine, with an emphasis on the Hindu tradition. Classical Ayurvedic texts including Carakasamhita and Susrutasamhita provide foundational assumptions about the body, the self, and gunas, which provide the underpinnings for the ethical system. Karma, the notion that every action has consequences, provides a foundation for medical morality. Conception, prolongation of one's blood-line is an important ethical aim of life. Thus a wide range of practices to further conception are acceptable. Abortion is a more complex matter ethically. At the end of life death is viewed in the context of passage to another life. Death is a relief from suffering to be coped with by the thought of an eternal atman or rebirth.


CSAR Benchmark Exercise 2013: Evaluation of Results from a Combined Computational Protein Design, Docking, and Scoring/Ranking Challenge.
Community Structure-Activity Resource (CSAR) conducted a benchmark exercise to evaluate the current computational methods for protein design, ligand docking, and scoring/ranking. The exercise consisted of three phases. The first phase required the participants to identify and rank order which designed sequences were able to bind the small molecule digoxigenin. The second phase challenged the community to select a near-native pose of digoxigenin from a set of decoy poses for two of the designed proteins. The third phase investigated the ability of current methods to rank/score the binding affinity of 10 related steroids to one of the designed proteins (pKd = 4.1 to 6.7). We found that 11 of 13 groups were able to correctly select the sequence that bound digoxigenin, with most groups providing the correct three-dimensional structure for the backbone of the protein as well as all atoms of the active-site residues. Eleven of the 14 groups were able to select the appropriate pose from a set of plausible decoy poses. The ability to predict absolute binding affinities is still a difficult task, as 8 of 14 groups were able to correlate scores to affinity (Pearson-r > 0.7) of the designed protein for congeneric steroids and only 5 of 14 groups were able to correlate the ranks of the 10 related ligands (Spearman-ρ > 0.7).


MDSCs in breast cancer: an important enabler of tumor progression and an emerging therapeutic target.
Women worldwide are more likely to develop breast cancer (BC) than any other type of cancer. The treatment of BC depends on the subtype and stage of the cancer, such as surgery, radiotherapy, chemotherapy, and immunotherapy. Although significant progress has been made in recent years, advanced or metastatic BC presents a poor prognosis, due to drug resistance and recurrences. During embryonic development, myeloid-derived suppressor cells (MDSCs) develop that suppress the immune system. By inhibiting anti-immune effects and promoting non-immune mechanisms such as tumor cell stemness, epithelial-mesenchymal transformation (EMT) and angiogenesis, MDSCs effectively promote tumor growth and metastasis. In various BC models, peripheral tissues, and tumor microenvironments (TME), MDSCs have been found to amplification. Clinical progression or poor prognosis are strongly associated with increased MDSCs. In this review, we describe the activation, recruitment, and differentiation of MDSCs production in BC, the involvement of MDSCs in BC progression, and the clinical characteristics of MDSCs as a potential BC therapy target.


Cloning of a cDNA encoding an ectoenzyme that degrades thyrotropin-releasing hormone.
Thyrotropin-releasing hormone (TRH) is an important extracellular signal substance that acts as a hypothalamic-releasing factor, which stimulates the release of adenohypophyseal hormones and functions as a neurotransmitter/neuromodulator in the central and peripheral nervous system. The inactivation of TRH after its release is catalyzed by an ectoenzyme localized preferentially on neuronal cells in the brain and on lactotrophic pituitary cells. This enzyme exhibits a very high degree of substrate specificity as well as other unusual properties. The activity of the adenohypophyseal enzyme is stringently controlled by estradiol and thyroid hormones, indicating that this enzyme itself may serve regulatory functions. Fragments of the enzyme isolated from rat or pig brain were generated by enzymatic digestion or cyanogen bromide cleavage, purified by reverse-phase HPLC, and sequenced. PCR amplification and screening of cDNA libraries from rat brain and pituitary led to the identification and isolation of a cDNA that encodes a protein of 1025 amino acids. The analysis of the deduced amino acid sequence was consistent with the identification of the enzyme as a glycosylated, membrane-anchored Zn metallopeptidase. Furthermore, Northern blot analysis demonstrated that the mRNA levels paralleled the tissue distribution of the enzyme and that in pituitary tissue the transcript levels rapidly increased when the animals were treated with triiodothyronine. Finally, transient transfection of COS-7 cells with this cDNA led to the expression of an active ectopeptidase that displayed the characteristics of the TRH-degrading ectoenzyme.


(4-Phenylalanine)oxytocin, an inhibitor of the antidiuretic effect of 8-arginine-vasopressin.
[4-Phenylalanine]oxytocin was prepared from Z-Cys(Bzl)-Tyr(Bzl)-Ile-Phe-Asn-Cys(Bzl)-Pro-Leu-Gly-NG2 (4) by deprotection with Na in NH3 followed by cyclization of the resulting disulfhydryl compound with ICH2CH2I. The protected peptide 4 was prepared from Boc-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 by the stepwise solution method. Coupling was effected by a modification of the dicyclohexylcarbodiimide-1-hydroxybenzotriazole preactivation method wherein the precipitate of dicyclohexylurea is removed by filtration prior to mixing of the amino and carboxyl components. The analog was found to be an effective inhibitor of the antidiuretic (ADH) response to exogenous arginine-vasopressin. It produced marked diuresis in the anti-ADH assay at approximately the same dose level as does [Leu4]oxytocin but, in contrast to [Leu4]oxytocin, showed natriuretic activity only at relatively high dose levels. In addition, [Phe4]oxytocin exhibited 0.15% of the oxytocic potency of oxytocin, weak antiavian vasodepressor activity (pA2 = 6.93), and no measurable rat pressor activity.


Rate and predictors of psychotic symptoms after Kashmir earthquake.
Psychotic symptoms are more common in general population than validated diagnosis of psychosis. There is evidence to suggest that these symptoms, hallucinations, paranoia, elated mood, thought insertion, are part of a spectrum of psychosis and may have association with the same risk factors that determine development of psychosis. These symptoms have an association with exposure to psychological trauma, post-traumatic stress disorder, anxiety and depression. The aim of this study was to explore the prevalence of psychotic symptoms in the population affected by a natural disaster, earthquake in this case and possible correlates of these symptoms. We conducted a cross-sectional survey of a population sample affected by the disaster, comprising of 1,291 individuals, 18 months after 2005 earthquake in Northern Pakistan and Kashmir to look at the prevalence of these symptoms and their correlates. Screening Instrument for Traumatic Stress in Earthquake Survivors and Self-Reporting Questionnaire and Psychosis Screening Questionnaire were used as tools. We examined association between the symptoms of anxiety, depression, PTSD and psychotic symptoms. We performed logistic regression analysis where hallucinations and delusions were dependent variables and demographic and trauma exposure variables were independent variables. The prevalence of psychotic symptoms ranged between 16.8 and 30.4 %. They were directly correlated with symptoms of post-traumatic stress disorder as well as concurrent symptoms of anxiety and depression. Lower level of education had a strong association in all the regression models. For hallucinations, living in a joint family had a negative association and participation in rescue, history of exposure to previous trauma and past psychiatric history had positive association. Paranoia was associated with female gender. Any psychiatric symptom was associated death of a family member, history of past psychiatric illness and living in a tent at the time of interview. Pattern of association of psychotic symptoms is consistent with prior literature and can be understood in the light of stress vulnerability model.


Direct characterization of hydrogen peroxide bleached thermomechanical pulp using spectroscopic methods.
The effects of thermomechanical pulp (TMP) bleaching with hydrogen peroxide under acidic and alkaline conditions were studied using different spectroscopic analytical methods. The results of hydroxyl radical determination in bleaching solutions, analyses of carbonyl and carboxyl groups contents in the pulp, and the cellulose fiber surface analysis by X-ray photoelectron spectroscopy (XPS) elucidate the chemistry of the hydrogen peroxide treatment. Diffuse reflectance laser flash photolysis (DRLFP) method showed the differences in the photochemical behavior that reflect the changes of the chromophoric system after the preliminary peroxide bleaching stage under acidic conditions. Fourier transform infrared (FTIR) spectroscopy confirmed the non-delignifying character of the bleaching process. Suppression of carbonyl and formation of carboxyl groups in the case of the two-stage peroxide bleaching performed in the presence of catalysts and stabilizers was also confirmed. FT-Raman studies showed the removal of coniferaldehyde groups after treatment under acidic and alkaline conditions.


Is Sensorineural Hearing Loss Related to Chronic Rhinosinusitis Caused by Outer Hair Cell Injury?
BACKGROUND Sensorineural hearing loss is caused by defects in the inner ear. In the present study, associations between chronic rhinosinusitis, outer hair cell injury, and sensorineural hearing loss were investigated. MATERIAL AND METHODS A total of 103 patients who met the inclusion criteria were recruited and allocated into a chronic rhinosinusitis group (n=82) and a simple deviated nasal septum group (n=21). Degree and type of hearing loss, including distortion product otoacoustic emissions, were used to assess the status of cochlear outer hair cells. RESULTS The rate of hearing loss in the simple deviated nasal septum group was significantly lower than in the chronic rhinosinusitis group (4.76%, 1/21 vs. 24.39%, 20/82, P<0.05), among which 15 chronic rhinosinusitis patients (75%, 15/20) had hearing loss in the high frequency range. Acoustic stapedial reflexes were elicited in all patients of the 2 groups, while positive Metz was found in 3 chronic rhinosinusitis patients (15%, 3/20). The pass rate of distortion product otoacoustic emissions (DPOAEs) for chronic rhinosinusitis patients was significantly lower than in simple deviated nasal septum patients (88.10% vs. 70.73%, P<0.05). Moreover, the signal-to-noise ratio of DPOAE test results at 704 Hz, 3991 Hz, and 5649 Hz in the chronic rhinosinusitis group were significantly lower than in the simple deviated nasal septum group (P<0.05). Logistic regression analysis revealed a correlation between severity of chronic rhinosinusitis and sensorineural hearing loss (OR=1.39, P<0.05). CONCLUSIONS Outer hair cell injury and sensorineural hearing loss may have a common cause in chronic rhinosinusitis patients.


Clinical characteristics of women with endometriosis.
The author followed prospectively the clinical presentation of endometriosis in 413 patients with subsequently confirmed endometriosis in 1994 laparotomies performed between 1984 and 1988. Age at menarche and at the time of clinical presentation of the disease, menstrual cycle abnormalities and the rest of the symptoms and signs of the condition, together with the findings on examination are presented. The correlations between the signs and symptoms and the clinical characteristics are presented by the author expand the previously published reports in the literature.


Prevalence and Normalization of Stress Urinary Incontinence in Female Strength Athletes.
Mahoney, K, Heidel, RE, and Olewinski, L. Prevalence and normalization of stress urinary incontinence in female strength athletes. J Strength Cond Res 37(9): 1877-1881, 2023-Strength training is increasing in popularity in women but is also a potential risk factor for stress urinary incontinence (SUI). There is potential for normalization of SUI in sports with high rates of SUI. Pelvic floor physical therapy is an effective treatment for SUI in both athletes and nonathletes, but female strength athletes may not be aware of this option. Our study sought to assess prevalence, normalization, rates of treatment, and preferred sources of information about SUI in female strength athletes. A novel cross-sectional survey was distributed online through social media groups dedicated to female strength athletes with 425 women responding within 4 days. Statistical significance of results was assumed at a 2-sided alpha value of 0.05. 43.5% of athletes experienced incontinence with daily tasks, 59.1% experienced incontinence with normal strength training, and 50.2% experienced incontinence during competition. Of the athletes who experienced incontinence, 61.4% did not have incontinence before starting their sport and only 9.4% had ever sought treatment. 67.9% of all athletes surveyed believed that urinary incontinence was a normal part of their sport. Our findings indicate that SUI is common in female strength athletes and may be a consequence of the sport itself. Normalization of SUI is common, and few athletes seek treatment.


Quality of life and general health of infertile women.
Measuring the quality of life (QOL) is a benchmark in today's world of medicine. The aim of the present study was to determine the general health and QOL of infertile women and certain affecting conditions. In a cross-sectional study, 161 infertile women referring to Dr. Rostami's Infertility Center of Shiraz, Southern Iran, in 2013 were enrolled by the convenience sampling method. Data were collected via a socio-demographic, general health (GHQ28), and the QOL Questionnaire of Infertile Couples and analyzed using descriptive and analytical statistics. According to 146 completely filled-out questionnaires, the mean age of the participants and their spouses were 29.4 ± 5.4 and 33.8 ± 5.8 years, respectively. Moreover, the general health of 57 (39%) patients was normal and that of 89 (61%) patients showed a degree of impairment. The scores for depression and physical symptoms were the highest and lowest, respectively. In addition, quite positive, positive, neutral, and negative specific QOL of infertile women were detected in 4 (2.8%), 72 (49.3%), 70 (47.9%), and 0 (0%) individuals, respectively. The total QOL scores had maximum correlation with GHQ anxiety (r = -0.596, P < 0.001) and general health scores had the highest correlation with physical QOL (r = -0.637, P < 0.001). The QOL was economically (P = 0.027), emotionally (P = 0.004), sexually (P = 0.017), physically (P = 0.037), and psychologically (P = 0.001) less for the women living in rural areas than other infertile women. However, university education (P = 0.015) and higher income per month (P = 0.008) had positive associations with QOL. General health of more than half of the infertile women indicated a degree of disorder. These women face the risk of anxiety, social dysfunction, and depression. Educational status, monthly income, and rural/urban residency are the major factors influencing the QOL.


Maternal circulating CD34+VEGFR-2+ and CD133+VEGFR-2+ progenitor cells increase during normal pregnancy but are reduced in women with preeclampsia.
Circulating endothelial progenitor cells (EPCs) may contribute to vascular endothelial cell homeostasis, and low levels of these cells are predictive of cardiovascular disease. We hypothesized that circulating EPCs increase in number during uncomplicated pregnancy but are reduced in women with preeclampsia. Peripheral blood was obtained from pregnant women and from nulligravidas in cross-sectional design. Cells expressing CD34 or CD133, in combination with vascular endothelial growth factor receptor-2 (VEGFR-2), were enumerated by flow cytometry. Both CD34(+)VEGFR-2(+) (doubly positive) and CD133(+)VEGFR-2( +) cells were significantly increased during the second and third trimesters of uncomplicated pregnancy compared to the first trimester. First trimester and nulligravida groups did not differ. Endothelial progenitor cells, quantified by flow cytometry or by circulating angiogenic cell (CAC) culture assay, were significantly reduced in women with preeclampsia compared to third trimester controls. Circulating EPCs appear to increase during normal pregnancy, and comparatively reduced numbers of these cells exist during preeclampsia.


Rosiglitazone and heart failure: the controversy and clinical implications.
In this issue of Congestive Heart Failure, the editor of this department addresses a topic on which there is conflicting data. Dr Tepper selected 2 of the most relevant abstracts for review. His comments on the conflicting data-and the polarized viewpoints among physicians that often result-provide insights on the clinical implications of the controversy.


Maternal modification of tissue antigenicity and the histocompatibility-2 (H-2) locus.
Differences in time of onset and severity of the secondary disease syndrome produced by the graft-versus-host reaction occurred in lethally irradiated reciprocal hybrid mice inoculated with bone marrow from parental strains of different H-2 genotypes. A less severe graft-versus-host reaction occurred when the marrow donor strain was syngeneic with the maternal strain of the hybrid. Differences in the survival pattern after inoculation of marrow from either parental strain were attributed to the quantitative difference in antigenicity control by the H-2 locus. The difference in the survival pattern between lethally irradiated reciprocal hybrid recipients inoculated with marrow of the same parental strain was attributed to reduced antigenicity as a result of a maternal modification of expression of paternally derived tissue antigens occurring during fetal development.


Outcomes Of Distal Femur Fracture Treated With Dynamic Condylar Screw.
Implants for open reduction and internal fixation of distal femoral fracture includes angle blade plate, rush nails, enders nail and interlocking nails. But all these devices are technically demanding and less effective in providing inter-fragmentary compression in osteoporotic bones. These problems can be solved with dynamic condylar screw (DCS).The objective of the study was to determine the frequency of different outcomes of distal femoral fracture treated with dynamic condylar screw. This case series study was carried out in the Department of Trauma & Orthopaedics, Ayub Teaching Hospital Abbottabad from 1st October 2014 to August 2015, after approval of the ethical committee of the institution. Data of all patients with distal femoral fractures aged 20-70 years, recruited through emergency, OPD or consultant clinic collected on a pro forma. Standard treatment of trauma was given to the patients. Detailed history was taken including the past medical and surgical history. Detailed examination including air-way, breathing and circulation, general physical examination and abdomino-pelvic examination was done in each patient. Investigations including urinalysis, haemoglobin %, full blood count, X-ray (both AP and lateral view) of the involved femur (including hip and knee) was done. Mean age of the patients was 43.18±14.647 ranging from 20 to 70 years. Mean duration of hospital stay in days was 2.21±1.111 ranging from 1 to 6 days. Patients' follow-up assessment after 4 months of surgery for union of femoral fracture treated with dynamic condylar screw was found in 96 (94.1%), wound infection was found in 7 (6.9%), knee stiffness was found in 21 (20.6%) and limb shortening was found in 7 (6.9%). Dynamic condylar screw is an easy, scientifically less difficult and satisfying method of treatment for fra.ctures of femur.


Antibodies to vesicular stomatitis New Jersey type virus in wild and domestic sentinel swine.
Wild sentinel swine on Ossabaw Island, Chatham County, Georgia, were serially bled and tested for vesicular stomatitis New Jersey type virus neutralizing antibody to determine the intensity, distribution, and progression of annual viral activity. From March through September, 1984 and 1985, 112 and 226 juvenile (less than 8 months) swine, respectively, were sampled. Seroconversions initially were detected on May 7, 1984 and May 18, 1985. Incidence of seroconversion in wild swine reached 32% during 1984 and 26% during 1985. Viral activity as determined by seroconversion results occurred earliest and was greatest on the southern half of Ossabaw Island. Domestic swine were housed in four pens under controlled conditions to document arthropod transmission of vesicular stomatitis virus. Twelve swine, three in each pen, were serially bled from April through September of both years. Seroconversion occurred during May 16-23, 1984 and May 15-22, 1985. Results varied among pen locations but were consistent between years. Clinical disease was not seen in any wild or domestic swine during either year.


Minimally invasive surgery: lateral approach interbody fusion: results and review.
A retrospective review of patients treated at 2 institutions with anterior lumbar interbody fusion using a minimally invasive lateral retroperitoneal approach, and review of literature. To analyze the outcomes from historical literature and from a retrospectively compiled database of patients having undergone anterior interbody fusions performed through a lateral approach. A paucity of published literature exists describing outcomes following lateral approach fusion surgery. Patients treated with extreme lateral interbody fusion (XLIF) were identified through retrospective chart review. Treatment variables included operating room (OR) time, estimated blood loss (EBL), length of hospital stay (LOS), complications, and fusion rate. A literature review, using the National Center for Biotechnology Information databases PubMed/MEDLINE and Google Scholar, yielded 14 peer-reviewed articles reporting outcomes scoring, complications, fusion status, long-term follow-up, and radiographic assessments related to XLIF. Published XLIF results were summarized and evaluated with current study data. A total of 84 XLIF patients were included in the current cohort analysis. OR time, EBL, and length of hospital stay averaged 199 minutes, 155 mL, and 2.6 days, respectively, and perioperative and postoperative complication rates were 2.4% and 6.1%. Mean follow-up was 15.7 months. Sixty-eight patients showed evidence of solid arthrodesis and no subsidence on computed tomography and flexion/extension radiographs. Results were within the ranges of those in the literature. Literature review identified reports of significant improvements in clinical outcomes scores, radiographic measures, and cost effectiveness. Current data corroborates and contributes to the existing body of literature describing XLIF outcomes. Procedures are generally performed with short OR times, minimal EBL, and few complications. Patients recover quickly, requiring minimal hospital stay, although transient hip/thigh pain and/or weakness is common. Long-term outcomes are generally favorable, with maintained improvements in patient-reported pain and function scores as well as radiographic parameters, including high rates of fusion.


Gentamicin Eluting 3D-Printed Implants for Preventing Post-Surgical Infections in Bone Fractures.
A surgically implantable device is an inevitable treatment option for millions of people worldwide suffering from diseases arising from orthopedic injuries. A global paradigm shift is currently underway to tailor and personalize replacement or reconstructive joints. Additive manufacturing (AM) has provided dynamic outflow to the customized fabrication of orthopedic implants by enabling need-based design and surface modification possibilities. Surgical grade 316L Stainless Steel (316L SS) is promising with its cost, strength, composition, and corrosion resistance to fabricate 3D implants. This work investigates the possibilities of application of the laser powder bed fusion (L-PBF) technique to fabricate 3D-printed (3DP) implants, which are functionalized with a multilayered antimicrobial coating to treat potential complications arising due to postsurgical infections (PSIs). Postsurgical implant-associated infection is a primary reason for implantation failure and is complicated mainly by bacterial colonization and biofilm formation at the installation site. PLGA (poly-d,l-lactide-co-glycolide), a biodegradable polymer, was utilized to impart multiple layers of coating using the airbrush spray technique on 3DP implant surfaces loaded with gentamicin (GEN). Various PLGA-based polymers were tested to optimize the ideal lactic acid: glycolic acid ratio and molecular weight suited for our investigation. 3D-Printed PLGA-GEN substrates sustained the release of gentamicin from the surface for approximately 6 weeks. The 3DP surface modification with PLGA-GEN facilitated cell adhesion and proliferation compared to control surfaces. The cell viability studies showed that the implants were safe for application. The 3DP PLGA-GEN substrates showed good concentration-dependent antibacterial efficacy against the common PSI pathogen Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis). The GEN-loaded substrates demonstrated antimicrobial longevity and showed significant biofilm growth inhibition compared to control. The substrates offered great versatility regarding the in vitro release rates, antimicrobial properties, and biocompatibility studies. These results radiate great potential in future human and veterinary clinical applications pertinent to complications arising from PSIs, focusing on personalized sustained antibiotic delivery.


[Enzymes in tumors of the breast. Histochemical study of the stroma in breast carcinomas].
The results obtained in histochemical examination of the stroma of mammary gland carcinomas allow to draws the following conclusions. The reaction for alkaline phosphatase proved suitable for detecting proliferation zones in the stroma of mammary gland carcinoma. Proliferation of fibroblasts, myofibroblasts, endothelial cells, and possibly also of other cells is involved. At present, myofibroblasts can not be cytoenzymatically differentiated from fibroblasts. The reactions for acid phosphatase and nonspecific esterase provide a quick and reliable picture on the amount of macrophages. The combined reaction for alkaline phosphatase and dipeptidylpeptidase IV in the same section indicates that individual segments of the newly formed capillary bed in the stroma of the tumor, i.e. the arterial, intermediary and venous segment, are differentially equipped by these enzymes. The activity of several enzymes in carcinomal stroma with typical stripe- and wave-like architecture can most probably be assigned to fibroblasts and myofibroblasts. Between the enzymatic activity in the stroma and the type or differentiation of the carcinoma no relationship was established.


A Novel Experimental Model of Colorectal Endometriosis.
Endometriosis is a disease that affects 6-10% of the female population, mainly women of reproductive age, and causes a variety of cyclic symptoms. Deep infiltrating endometriosis and in particular bowel involvement presents a challenge for modern surgery. To date, there are no experimental animal models in this field, demonstrating experimental induction of endometriosis directly attached to surface of the colon imitating human colorectal endometriosis; hence, the implementation of novel pharmaceutical and surgical strategies for the management of colorectal endometriosis is mainly limited to clinical studies. To investigate whether induction of colorectal endometriotic lesions in is feasible in rats. Twenty, female, adult, non-pregnant Sprague Dawley rats sustained uterine horn resection, which was then placed around the rectum of the rat with the endometrial surface in direct contact with the bowel serosa and approximated in the serosal surface of the colon with two sutures. Two weeks following, surgery rats were euthanized and the bowel was surgically explored. The presence of a cystic lump at the site of the surgical intervention was evaluated macroscopically and microscopically. Histopathology documented the presence of cystic endometriosis. The endometriotic focus was adherent to the bowel wall by large fibrous nodules with concomitant replacement of part of the outer longitudinal muscle layer. The findings of our study support that the proposed experimental model of colorectal endometriosis is feasible, easily reproducible and may be implemented in future research in this field.


The secreted frizzled related protein 2 (SFRP2) gene is a target of the Pax2 transcription factor.
Despite their essential role in vertebrate development, the function of Pax proteins in gene regulation is not well understood. To identify potential genes regulated by the Pax2 protein, we screened embryonic kidney cells transformed with Pax2-expressing retroviruses for genes activated in response to Pax2 expression. In this system, the gene encoding the secreted frizzled related protein, Sfrp2, was strongly activated in all Pax2b-expressing cells. This activation of Sfrp2 expression correlated with changes in chromatin structure at the Sfrp2 locus, particularly in and around regions of Pax2 binding. Although the amount of Pax2-dependent transactivation was low in transient assays, the data suggests that local alterations of chromatin structure by Pax proteins can greatly enhance expression when presented in the right cellular context.


Metabolomics analysis of Pulsatilla decoction on treatment of wetness-heat-induced diarrhea in rats based on UPLC-Q/TOF-MS/MS.
Pulsatilla decoction (PD) is a classical prescription in traditional Chinese medicine that has therapeutic effects on wetness-heat-induced diarrhea (WHD). To investigate the therapeutic effects of PD in the treatment of WHD and elucidate the potential mechanism, we used a metabolomics strategy on the base of ultraperformance liquid chromatography coupled with quadrupole time-of-flight/mass spectrometry (UPLC-Q/TOF-MS/MS) and analyzed the serum samples of 32 rats to identify differential metabolites and pathways associated with the PD treatment of WHD. With variable importance for projection >1.0 in the Orthogonal partial least-squares discriminant analysis (OPLS-DA ) models and FC ≥1.2 or ≤0.8, 67 differential metabolites in the model and control groups and 33 differential metabolites in the model and PD groups were screened. A total of 23 differential metabolites were selected based on Venny analysis. Functional analysis showed that the differential metabolites identified were primarily involved in pentose and glucuronate interconversions, glycerophospholipid metabolism, tryptophan metabolism, starch and sucrose metabolism, and glycerolipid metabolism. This study suggested that PD exerts inhibitory effects on WHD. In particular, the significant roles of PD for treating WHD lie in regulating perturbed energy metabolism, glycerophospholipid metabolism and glycerolipid metabolism, and promoting lysoPC production restoring the function of intestinal tract.


Does nitric oxide mediate the vasodilator activity of nitroglycerin?
Nitroglycerin (glyceryl trinitrate, GTN) relaxes blood vessels primarily via activation of the soluble guanylyl cyclase (sGC)/cGMP/cGMP-dependent protein kinase (cGK-I) pathway. Although the precise mechanism of sGC activation by GTN in the vascular wall is unknown, the mediatory role of nitric oxide (NO) has been postulated. We tested the GTN/NO hypothesis in different types of isolated rat and rabbit blood vessels using two novel approaches: (1) EPR spin trapping using colloid Fe(DETC)2 and (2) analysis of cGK-I-dependent phosphorylation of the vasodilator-stimulated phosphoprotein at Ser239 (P-VASP). For comparison, another organic nitrate, isosorbide dinitrate (ISDN), and endothelium-dependent vasodilator, calcium ionophore A23187, were tested. We found a marked discrepancy between GTN's strong vasoactivity (vasodilation and augmentation of P-VASP) and its poor NO donor properties. In aortas precontracted with phenylephrine, GTN, ISDN, and A23187 induced nearly full relaxations (>80%) and doubling of vascular P-VASP content at concentrations of 100 nmol/L, 100 micromol/L, and 1 micromol/L, respectively. GTN applied in vasorelaxant concentrations (10 to 1000 nmol/L) did not significantly increase the basal vascular NO production, in contrast to ISDN and A23187. The absence of GTN-derived NO was confirmed in rabbit vena cava and renal artery. A significant increase in vascular NO formation was observed only at suprapharmacological GTN concentrations (>10 micromol/L). The concentration dependency of NO formation from GTN was comparable to that of ISDN, although the latter exhibits 100-folds lower vasorelaxant potency. We conclude that GTN activates the sGC/cGMP/cGK-I pathway and induces vasorelaxation without intermediacy of the free radical NO. The full text of this article is available online at http://www.circresaha.org.


Microfluidics-Based Biosensors: A Microfluidic Paper-Based Origami Nanobiosensor for Label-Free, Ultrasensitive Immunoassays (Adv. Healthcare Mater. 11/2016).
The first microfluidic paper-based origami nano-biosensor featuring zinc oxide nanowires and an electrochemical impedance spectroscopy biosensing mechanism, for label-free, ultrasensitive immunoassays is reported by X. Li and X. Liu on page 1326. The sensor consists of cellulose paper, a carbon ink electrode, and zinc oxide nanowires directly grown on the top. Possible parallelization of assays and high storage stability render the sensor promising for clinical diagnostics applications.


Evidence for large complex networks of plant short silencing RNAs.
In plants and animals there are many classes of short RNAs that carry out a wide range of functions within the cell; short silencing RNAs (ssRNAs) of 21-25 nucleotides in length are produced from double-stranded RNA precursors by the protein Dicer and guide nucleases and other proteins to their RNA targets through base pairing interactions. The consequence of this process is degradation of the targeted RNA, suppression of its translation or initiation of secondary ssRNA production. The secondary ssRNAs in turn could then initiate further layers of ssRNA production to form extensive cascades and networks of interacting RNA [1]. Previous empirical analysis in plants established the existence of small secondary ssRNA cascade [2], in which a single instance of this event occurred but it was not known whether there are other more extensive networks of secondary sRNA production. We generated a network by predicting targets of ssRNA populations obtained from high-throughput sequencing experiments. The topology of the network shows it to have power law connectivity distribution, to be dissortative, highly clustered and composed of multiple components. We also identify protein families, PPR and ULP1, that act as hubs within the network. Comparison of the repetition of genomic sub-sequences of ssRNA length between Arabidopsis and E.coli suggest that the network structure is made possible by the underlying repetitiveness in the genome sequence. Together our results provide good evidence for the existence of a large, robust ssRNA interaction network with distinct regulatory function. Such a network could have a massive effect on the regulation of gene expression via mediation of transcript levels.


Baumard et al.'s moral markets lack market dynamics.
Market models are indeed indispensable to understanding the evolution of cooperation and its emotional substrates. Unfortunately, Baumard et al. eschew market thinking in stressing the supposed invariance of moral/cooperative behavior across circumstances. To the contrary, humans display contingent morality/cooperation, and these shifts are best accounted for by market models of partner choice for mutually beneficial collaboration.


Phospholipid bilayer nanodiscs: a powerful tool to study the structural organization and biochemical reactivity of proteins in membrane-like environments.
Nanodiscs are disc-like structures formed by two copies of a membrane scaffold protein, engineered from apolipoprotein A-I, surrounding a phospholipid mixture that can incorporate membrane proteins preserving their natural properties. They behave as soluble entities allowing the use of high-resolution structural techniques to determine the structural organization of the embedded membrane protein, and the use of solution biochemical-biophysical tools to measure its activity, assembly and interactions with other proteins in membranelike environments. In addition, nanodiscs are biocompatible which makes them an attractive technology to be used in therapy, drug discovery, and other biotechnological applications.


Home blood pressure monitoring in diabetic population.
Normalization of blood pressure is today as necessary as an optimal blood glucose control. These targets aim at reducing the negative consequences of hypertension which is particularly frequent and of poor prognosis for these patients. Nevertheless, the definition of the real blood pressure of these patients is uneasy because of the lack of precision of clinical blood pressure measurement. New methods have been developed to address this insufficiency. Home blood pressure monitoring is characterised by good compliance and accuracy, but patient education needs a special training and validated automated devices. This method has to be proposed to the diabetic population as soon as hypertension may be a problem. These patients will contribute to monitor their own blood pressure as they do it with blood glucose control.


Patching the Pathway and Widening the Pipeline: Models for Developing a Diverse Early Childhood Workforce in Chicago.
With the growing appreciation of the importance of early learning experiences for children's healthy development, attention to the cultivation and maintenance of a qualified workforce has steadily increased. Such a workforce must have not just the knowledge and skills related to child development and early learning, but also be linguistically and culturally prepared to meet the needs of an increasingly diverse child and family population. To ensure a highly qualified workforce, programs and policymakers must attend to both the "pipeline" through which new early childhood educators (ECEs) enter the workforce and the "pathways" by which ECEs work toward and obtain the necessary education and credentials for different roles within the field. In line with the aims of this special issue, this paper leverages the first-person account style to describe barriers to and creative solutions for the development of practitioners in low-resourced communities in Chicago, with the goal of informing practice and policy. We describe three prior and ongoing partnership programs between community-based organizations and institutions of higher education, each tailored to support a unique population in the ECE pipeline on the pathway for increased educational attainment and credentialing. Each program is grounded in a specific community of Chicago, a diverse city with a sizable population of children raised in non-English speaking homes. Each program addresses specific needs of the communities they serve, especially around the recruitment, retention, and promotion of bilingual ECEs. Program administrators and community members describe each programs' goals, development, and key components unique to their target population as well as key takeaways. We conclude with an overview of critical components that we identified across these programs in order to create pathways for change within the workforce and the communities they serve.


Prone positioning for severe ARDS in a postpartum COVID-19 patient following caesarean section.
A 31-year-old pregnant woman presented with symptomatic COVID-19, which was complicated by progressive hypoxaemia requiring intensive care and emergent delivery by caesarean section. Afterward, she was successfully supported with mechanical ventilation and prone positioning and ultimately recovered. We review literature regarding complications of COVID-19 affecting pregnancy and evidence-based treatment strategies.


Generative Topographic Mapping (GTM): Universal Tool for Data Visualization, Structure-Activity Modeling and Dataset Comparison.
Here, the utility of Generative Topographic Maps (GTM) for data visualization, structure-activity modeling and database comparison is evaluated, on hand of subsets of the Database of Useful Decoys (DUD). Unlike other popular dimensionality reduction approaches like Principal Component Analysis, Sammon Mapping or Self-Organizing Maps, the great advantage of GTMs is providing data probability distribution functions (PDF), both in the high-dimensional space defined by molecular descriptors and in 2D latent space. PDFs for the molecules of different activity classes were successfully used to build classification models in the framework of the Bayesian approach. Because PDFs are represented by a mixture of Gaussian functions, the Bhattacharyya kernel has been proposed as a measure of the overlap of datasets, which leads to an elegant method of global comparison of chemical libraries.


Complete Genome Sequence of Citrobacter freundii Myophage Merlin.
Bacteriophage Merlin is a T4-like myophage which infects Citrobacter freundii, a member of the Enterobacteriaceae family. C. freundii is an opportunistic pathogen that is a common cause of nosocomial infections. This report announces the complete genome of myophage Merlin and describes its features.


Current Considerations for Clinical Management and Care of People with HIV: Findings from the 11th Annual International HIV and Aging Workshop.
The number of people with HIV (PWH) aged 50 years or older continues to steadily increase. The convergence of age- and HIV-related complications in these individuals presents a challenge for both patients and clinicians alike. New findings continue to emerge, as numerous researchers evaluate the combined impact of these two factors on quality of life, physiological systems, and mental health in PWH. Since its first occurrence in 2009, the International Workshop on HIV and Aging has served as a multidisciplinary meeting to share basic biomedical data, clinical trial results, treatment strategies, and epidemiological recommendations, toward better understanding and outcomes among like-minded scientific professionals. In this article, we share a selection of key findings presented in plenary talks at the 11th Annual International Workshop on HIV and Aging, held virtually from September 30, 2020 to October 2, 2020. We will also address the future directions of HIV and aging research, to further assess how the aging process intersects with chronic HIV.


(18)F-DPA-714 PET Imaging for Detecting Neuroinflammation in Rats with Chronic Hepatic Encephalopathy.
Neuroinflammation is considered to be the pathogenesis of hepatic encephalopathy (HE), and imaging neuroinflammation is implicated in HE management. (11)C-PK11195, a typical translocator protein (TSPO) radiotracer, is used for imaging neuroinflammation. However, it has inherent limitations, such as short half-life and limited availability. The purpose of this study was to demonstrate the efficiency of new generation TSPO radiotracer, (18)F-DPA-714, in detecting and monitoring neuroinflammation of chronic HE. This study was divided into two parts. The first part compared (18)F-DPA-714 and (11)C-PK11195 radiotracers in ten HE induced rats [bile duct ligation (BDL) and fed hyperammonemic diet (HD)] and 6 control rats. The animal subjects underwent dynamic positron emission tomography (PET) during 2-day intervals. The (11)C-PK11195 PET study showed no differences in whole brain average percent injected dose per gram (%ID/g) values at all time points (all P>0.05), while the (18)F-DPA-714 PET study showed higher whole brain average %ID/g values in HE rats compared to control group rats at 900 s to 3300 s after injecting radiotracer (all P<0.05). The second part of the study evaluated the effectiveness of ibuprofen (IBU) treatment to chronic HE. Forty rats were classified into six groups, including Sham+normal saline (NS), Sham+IBU, BDL+NS, BDL+HD+NS, BDL+IBU, and BDL+HD+IBU groups. (18)F-DPA-714 PET was used to image neuroinflammation. Whole and regional brain average %ID/g values, neurological features, inflammatory factors and activated microglia showed better in the IBU groups than in the NS groups (all P<0.05) and no difference was seen in the Sham groups compared to IBU groups (all P>0.05). In conclusion, this study demonstrated that (18)F-DPA-714 is an ideal TPSO radiotracer for imaging neuroinflammation and monitoring anti-neuroinflammation treatment efficacy of chronic HE.


Electrospinning of poly(L-lactide) nanofibers encapsulated with water-soluble fullerenes for bioimaging application.
Photoluminescent fullerene nanoparticles/nanofibers have potential applications in bioimaging. A novel fluorescent nanofibrous material, consisting of fullerene nanoparticles and poly(L-lactide) (PLLA), was fabricated via a simple electrospinning method, and the composite nanofibers were characterized by various techniques such as scanning electron microscopy (SEM), laser scanning confocal microscopy (LSCM), and transmission electron microscopy (TEM). The nanofibers were uniform, and their surfaces were reasonably smooth, with the average diameters of fibers ranging from 300 to 600 nm. The fullerene nanoparticles were encapsulated within the composite nanofibers, forming a core-shell structure. The nanofiber scaffolds showed excellent hydrophilic surface due to the addition of water-soluble fullerene nanoparticles. The composite nanofibers used as substrates for bioimaging in vitro were evaluated with human liver carcinoma HepG2 cells, the fullerene nanoparticles signal almost displayed in every cell, implying the potential of fluorescent fullerene nanoparticles/PLLA nanofibers to be used as scaffolds for bioimaging application.


Herpes Simplex Virus 1 UL34 Protein Regulates the Global Architecture of the Endoplasmic Reticulum in Infected Cells.
Upon herpes simplex virus 1 (HSV-1) infection, the CD98 heavy chain (CD98hc) is redistributed around the nuclear membrane (NM), where it promotes viral de-envelopment during the nuclear egress of nucleocapsids. In this study, we attempted to identify the factor(s) involved in CD98hc accumulation and demonstrated the following: (i) the null mutation of HSV-1 UL34 caused specific dispersion throughout the cytoplasm of CD98hc and the HSV-1 de-envelopment regulators, glycoproteins B and H (gB and gH); (ii) as observed with CD98hc, gB, and gH, wild-type HSV-1 infection caused redistribution of the endoplasmic reticulum (ER) markers calnexin and ERp57 around the NM, whereas the UL34-null mutation caused cytoplasmic dispersion of these markers; (iii) the ER markers colocalized efficiently with CD98hc, gB, and gH in the presence and absence of UL34 in HSV-1-infected cells; (iv) at the ultrastructural level, wild-type HSV-1 infection caused ER compression around the NM, whereas the UL34-null mutation caused cytoplasmic dispersion of the ER; and (v) the UL34-null mutation significantly decreased the colocalization efficiency of lamin protein markers of the NM with CD98hc and gB. Collectively, these results indicate that HSV-1 infection causes redistribution of the ER around the NM, with resulting accumulation of ER-associated CD98hc, gB, and gH around the NM and that UL34 is required for ER redistribution, as well as for efficient recruitment to the NM of the ER-associated de-envelopment factors. Our study suggests that HSV-1 induces remodeling of the global ER architecture for recruitment of regulators mediating viral nuclear egress to the NM.IMPORTANCE The ER is an important cellular organelle that exists as a complex network extending throughout the cytoplasm. Although viruses often remodel the ER to facilitate viral replication, information on the effects of herpesvirus infections on ER morphological integrity is limited. Here, we showed that HSV-1 infection led to compression of the global ER architecture around the NM, resulting in accumulation of ER-associated regulators associated with nuclear egress of HSV-1 nucleocapsids. We also identified HSV-1 UL34 as a viral factor that mediated ER remodeling. Furthermore, we demonstrated that UL34 was required for efficient targeting of these regulators to the NM. To our knowledge, this is the first report showing that a herpesvirus remodels ER global architecture. Our study also provides insight into the mechanism by which the regulators for HSV-1 nuclear egress are recruited to the NM, where this viral event occurs.


Thermodynamics and kinetics of the glyoxylate cycle.
Because the standard Gibbs energies of formation of all the species of reactants in the glyoxylate cycle are known at 298.15 K, it is possible to calculate the apparent equilibrium constants of the five reactions in the cycle in the pH range 5-9 and ionic strengths from 0 to approximately 0.35 M. In making calculations on such a system, it is convenient to specify concentrations of coenzymes like NADox and NADred because they are involved in many reactions and may be in steady states. Calculations are given for [NADox] = 1000[NADred] and [NADox] = 10[NADred]. Equilibrium compositions are calculated using computer programs when all the reactants are present initially and when only glyoxylate and CoA are present initially. The kinetics of the reactions in the glyoxylate cycle at specified concentrations of NADox and NADred are calculated by numerical solution of the steady-state rate equations for the case where the reactant concentrations are below their Michaelis constants and only glyoxylate and CoA are present initially.


Characterization of a rare mosaic X-ring chromosome in a patient with Turner syndrome.
Ring chromosomes can be formed by terminal breaks of two arms of a chromosome and their rejoining, leading to a loss of genetic material. They may also be formed by telomere-telomere fusions with no deletion, resulting in the formation of a complete ring. Mosaic X-ring chromosomes are extremely rare and have highly variable phenotypes. Here, we report a case with a mosaic X-ring chromosome in a patient with Turner syndrome, and we illustrate the unreported complicated mechanism using chromosome analysis and fluorescence in situ hybridization (FISH). A 10-year-old girl of short stature presenting Turner syndrome was admitted to our hospital. The patient's clinical characteristics were subsequently documented. Genetic analysis showed a karyotype of mostly 45,X[140]/46,X,r(X)[60]. The X ring chromosome was cytogenetically characterized as 45,X/46,X,r(X)(p22.32q21.1), with a length of approximately 74 Mb. Taken together, we report a rare case with a mosaic X ring chromosome in Turner syndrome and we believe this case expands our collective knowledge of mosaic structural chromosomal disorders and provides new insight into clinical management and genetic counseling for Turner syndrome.


A CLN2-related and thermostable serine-carboxyl proteinase, kumamolysin: cloning, expression, and identification of catalytic serine residue.
The gene encoding kumamolysin, a thermostable pepstatin-insensitive carboxyl proteinase, was cloned and expressed. (i) Kumamolysin was synthesized as a large precursor consisting of two regions: amino-terminal prepro (188 amino acids) and mature proteins (384 amino acids). (ii) The deduced amino acid sequence of the mature region exhibited high similarity to those of such bacterial pepstatin-insensitive enzymes as Pseudomonas carboxyl proteinase (PSCP; EC 18.104.22.168, identity = 37%), Xanthomonas carboxyl proteinase (XCP; EC 220.127.116.11, identity = 36%), and human CLN2 gene product (identity = 36%), which is related to a fatal neurodegenerative disease. (iii) The presumed catalytic triad, Glu78, Asp82, Ser278 [three-dimensional structure of PSCP: Wlodawer, A. et al. (2001) Nature Struct. Biol., 8, 442-446], was found to be conserved in the amino acid sequence of kumamolysin. (iv) Kumamolysin was inactivated by such aldehyde-type inhibitors as Ac-Ile-Pro-Phe-CHO (K(i) = 0.7 0.14 microM). In PSCP, it has been clarified that these inhibitors form a hemiacetal linkage with the catalytic serine residue and inactivate the enzyme. (v) Mutational analysis of the Ser278 residue revealed that the mutant lost both auto-processing activity and proteolytic activity. These results strongly suggest that kumamolysin has a unique catalytic triad consisting of Glu78, Asp82, and Ser278 residues, as previously observed for PSCP.


Union transitions and changes in BMI among adults in Mexico.
This study utilizes nationally representative, longitudinal data from the Mexico Family Life Survey to examine the associations between union transitions and changes in body mass index (BMI) among adults in Mexico. Results from change score regression models (N = 11,339) indicate larger BMI gains for those entering a union than for those remaining single, net of baseline weight status and socioeconomic controls. Further, a significant moderating effect of baseline weight status suggests that overweight individuals entering a union gain almost two BMI points more than overweight single individuals during this three-year period. Individuals experiencing a union dissolution gain less BMI than those entering a union, but are predicted to lose BMI (as found in the United States) only if they are overweight before the transition.


Functional repair of human donor lungs by IL-10 gene therapy.
More than 80% of potential donor lungs are injured during brain death of the donor and from complications experienced in the intensive care unit, and therefore cannot be used for transplantation. These lungs show inflammation and disruption of the alveolar-capillary barrier, leading to poor gas exchange. Although the number of patients in need of lung transplantation is increasing, the number of donors is static. We investigated the potential to use gene therapy with an adenoviral vector encoding human interleukin-10 (AdhIL-10) to repair injured donor lungs ex vivo before transplantation. IL-10 is an anti-inflammatory cytokine that mainly exerts its suppressive functions by the inactivation of antigen-presenting cells with consequent inhibition of proinflammatory cytokine secretion. In pigs, AdhIL-10-treated lungs exhibited attenuated inflammation and improved function after transplantation. Lungs from 10 human multiorgan donors that had suffered brain death were determined to be clinically unsuitable for transplantation. They were then maintained for 12 hours at body temperature in an ex vivo lung perfusion system with or without intra-airway delivery of AdhIL-10 gene therapy. AdhIL-10-treated lungs showed significant improvement in function (arterial oxygen pressure and pulmonary vascular resistance) when compared to controls, a favorable shift from proinflammatory to anti-inflammatory cytokine expression, and recovery of alveolar-blood barrier integrity. Thus, treatment of injured human donor lungs with the cytokine IL-10 can improve lung function, potentially rendering injured lungs suitable for transplantation into patients.


Cochlear implantation impairs intracochlear microcirculation and counteracts iNOS induction in guinea pigs.
Preservation of residual hearing remains a great challenge during cochlear implantation. Cochlear implant (CI) electrode array insertion induces changes in the microvasculature as well as nitric oxide (NO)-dependent vessel dysfunction which have been identified as possible mediators of residual hearing loss after cochlear implantation. A total of 24 guinea pigs were randomized to receive either a CI (n = 12) or a sham procedure (sham) by performing a cochleostomy without electrode array insertion (n = 12). The hearing threshold was determined using frequency-specific compound action potentials. To gain visual access to the stria vascularis, a microscopic window was created in the osseous cochlear lateral wall. Cochlear blood flow (CBF) and cochlear microvascular permeability (CMP) were evaluated immediately after treatment, as well as after 1 and 2 h, respectively. Finally, cochleae were resected for subsequent immunohistochemical analysis of the iNOS expression. The sham control group showed no change in mean CBF after 1 h (104.2 ± 0.7%) and 2 h (100.8 ± 3.6%) compared to baseline. In contrast, cochlear implantation resulted in a significant continuous decrease in CBF after 1 h (78.8 ± 8.1%, p < 0.001) and 2 h (60.6 ± 11.3%, p < 0.001). Additionally, the CI group exhibited a significantly increased CMP (+44.9% compared to baseline, p < 0.0001) and a significant increase in median hearing threshold (20.4 vs. 2.5 dB SPL, p = 0.0009) compared to sham after 2 h. Intriguingly, the CI group showed significantly lower iNOS-expression levels in the organ of Corti (329.5 vs. 54.33 AU, p = 0.0003), stria vascularis (596.7 vs. 48.51 AU, p < 0.0001), interdental cells (564.0 vs. 109.1 AU, p = 0.0003) and limbus fibrocytes (119.4 vs. 18.69 AU, p = 0.0286). Mechanical and NO-dependent microvascular dysfunction seem to play a pivotal role in residual hearing loss after CI electrode array insertion. This may be facilitated by the implantation associated decrease in iNOS expression. Therefore, stabilization of cochlear microcirculation could be a therapeutic strategy to preserve residual hearing.


Constipation in Pediatrics: A Clinical Review.
Constipation is a common problem encountered in the pediatric setting. For many children, constipation is functional in nature-potentially stemming from a pattern of stool output that is infrequent or not fully productive (ie, incomplete stool evacuation)-and includes behavioral concerns like stool withholding. In many cases of functional constipation (FC), the pattern may have started in the toddler years during or before toilet training and may now be well established. Additional factors often include inadequate fluids and fiber, or excess dietary dairy or carbohydrates. In a small percentage of cases, constipation is a symptom of an underlying organic disease process. Laboratory tests and imaging may be helpful in determining most organic concerns. In the absence of an organic process, FC can be treated by properly educating families about the nature of FC as well as careful attention to dietary fiber and fluid intake, use of stool softeners, laxatives, and behavioral modifications. [Pediatr Ann. 2021;50(8):e320-e324.].


Metabolites of fungi & actinomycetes active against mosquito larvae.
Extracellular secondary metabolites from 350 fungi and 94 actinomycetes were screened for larvicidal activity against Culex quinquefasciatus, Anopheles stephensi and Aedes aegypti. Of them, 133 fungal metabolites and 35 from actinomycetes were active. Two from Streptomyces sp. and one from Paecilomyces sp. were highly active with LC50 value of 1-3 microliters/ml. The metabolites were more toxic to C. quinquefasciatus than to A. stephensi or Ae. aegypti larvae.


Salt excess causes left ventricular diastolic dysfunction in rats with metabolic disorder.
Metabolic syndrome is a highly predisposing condition for cardiovascular disease and could be a cause of excess salt-induced organ damage. Recently, several investigators have demonstrated that salt loading causes left ventricular diastolic dysfunction associated with increased oxidative stress and mineralocorticoid receptor activation. We, therefore, investigated whether excess salt induces cardiac diastolic dysfunction in metabolic syndrome via increased oxidative stress and upregulation of mineralocorticoid receptor signals. Thirteen-week-old spontaneously hypertensive rats and SHR/NDmcr-cps, the genetic model of metabolic syndrome, were fed a normal salt (0.5% NaCl) or high-salt (8% NaCl) diet for 4 weeks. In SHR/NDmcr-cps, salt loading induced severe hypertension, abnormal left ventricular relaxation, and perivascular fibrosis. Salt-loaded SHR/NDmcr-cps also exhibited overproduction of reactive oxygen species and upregulation of mineralocorticoid receptor-dependent gene expression, such as Na(+)/H(+) exchanger-1 and serum- and glucocorticoid-inducible kinase-1 in the cardiac tissue. However, in spontaneously hypertensive rats, salt loading did not cause these cardiac abnormalities despite a similar increase in blood pressure. An antioxidant, tempol, prevented salt-induced diastolic dysfunction, perivascular fibrosis, and upregulation of mineralocorticoid receptor signals in SHR/NDmcr-cps. Moreover, a selective mineralocorticoid receptor antagonist, eplerenone, prevented not only diastolic dysfunction but also overproduction of reactive oxygen species in salt-loaded SHR/NDmcr-cps. These results suggest that metabolic syndrome is a predisposed condition for salt-induced left ventricular diastolic dysfunction, possibly via increased oxidative stress and enhanced mineralocorticoid receptor signals.


Rotational Signatures of Dispersive Stacking in the Formation of Aromatic Dimers.
The aggregation of aromatic species is dictated by inter- and intramolecular forces. Not only is characterizing these forces in aromatic growth important for understanding grain formation in the interstellar medium, but it is also imperative to comprehend biological functions. We report a combined rotational spectroscopic and quantum-chemical study on three homo-dimers, comprising of diphenyl ether, dibenzofuran, and fluorene, to analyze the influence of structural flexibility and the presence of heteroatoms on dimer formation. The structural information obtained shows clear similarities between the dimers, despite their qualitatively different molecular interactions. All dimers are dominated by dispersion interactions, but the dibenzofuran dimer is also influenced by repulsion between the free electron pairs of the oxygen atoms and the π-clouds. This study lays the groundwork for understanding the first steps of molecular aggregation in systems with aromatic residues.


Coronary microvascular disease as an early culprit in the pathophysiology of diabetes and metabolic syndrome.
Metabolic syndrome (MetS) is a group of cardio-metabolic risk factors that includes obesity, insulin resistance, hypertension, and dyslipidemia; these are also a combination of independent coronary artery disease (CAD) risk factors. Alarmingly, the prevalence of MetS risk factors are increasing and a leading cause for mortality. In the vasculature, complications from MetS and type 2 diabetes (T2D) can be divided into microvascular (retinopathy and nephropathy) and macrovascular (cardiovascular diseases and erectile dysfunction). In addition to vascular and endothelial dysfunction, vascular remodeling and stiffness are also hallmarks of cardiovascular disease (CVD), and well-characterized vascular changes that are observed in the early stages of hypertension, T2D, and obesity [1-3]. In the heart, the link between obstructive atherosclerosis of coronary macrovessels and myocardial ischemia (MI) is well established. However, recent studies show that abnormalities in the coronary microcirculation are associated with functional and structural changes in coronary microvessels (classically defined as being ≤150-200μm internal diameter), which may cause or contribute to MI even in the absence of obstractive CAD. This suggests a prognostic value of an abnormal coronary microcirculation as an early sub-clinical culprit in the pathogenesis and progression of heart disease in T2D and MetS. The aim of this review is to summarize recent studies investigating the coronary microvascular remodeling in an early pre-atherosclerotic phase of MetS and T2D, and to explore potential mechanisms associated with the timing of coronary microvascular remodeling relative to that of the macrovasculature.


[Application of two and three-dimensional ultrasound measurement of fetal thymus in fetal intrauterine growth restriction].
To measure the ultrasonic parameters of transverse diameter, anteroposterior diameter and volume of fetal thymus through two and three-dimensional (2D and 3D) probes, establish normal reference range of fetal thymus development and assess the correlation between fetal intrauterine growth restriction and fetal thymus development. A total of 53 patients with suspected fetal intrauterine growth restriction (IUGR) at our hospital from December 2012 to May 2014 were selected into the observation group while another 53 cases as the control group corresponding to the former group's gestational week (GA). The transverse and anteroposterior diameters were measured in the three vessel view by 2D-ultrasound and the volume of fetal thymus was measured through 3D ultrasound. The control parameters were analyzed by linear regression analysis. And two groups of parameters were tested by rank sum test. P < 0.05 was deemed significant. The regression equation of fetal thymus transverse diameter and GA was: Y = 0.14X-1.174, R² = 0.766, P < 0.05; the regression equation of fetal thymus anteroposterior diameter and GA was: Y = 0.49X-0.166, R² = 0.792, P < 0.05; the regression equation of fetal thymus volume and GA was: Y = 0.652X-10.611, R² = 0.791, P < 0.05. Two groups underwent rank sum test of fetal thymus transverse diameter, anteroposterior diameter and volume (P < 0.05). Fetal thymus transverse diameter, anteroposterior diameter and volume increase with gestational weeks. In IUGR, fetal thymus transverse diameter, anteroposterior diameter and volume are less than those of the same GA fetal thymus.


New developments in colorectal surgery.
Surgical management of diseases of the colon and rectum continues to evolve. This review examines the recent publications that have led to or may lead to changes in practice in this field. We identified and reviewed the recent publications in the areas of colon, rectal, and anal cancers; inflammatory bowel disease; incontinence; diverticulitis; hemorrhoids; fistulas; and quality improvement initiatives. New technologies and novel questions have changed practice and will improve patient outcomes. Multiinstitutional studies, ideally randomized, continue to be essential to answer the questions that will lead to identification of best practices.


New peptides of the polycomb group protein enhancer of zeste homolog 2 with the potential to induce cancer-reactive cytotoxic T lymphocytes in human leukocyte antigen-A2+ prostate cancer patients.
The polycomb group protein enhancer of zeste homolog 2 (EZH2) is linked to aggressive prostate cancer and could be an appropriate target in specific immunotherapy. In this study, we attempted to identify EZH2-derived peptides that have the potential to generate cancer-reactive cytotoxic T lymphocytes (CTLs) in human leukocyte antigen (HLA)-A2+ prostate cancer patients. Twelve EZH2-derived peptides were prepared based on the HLA-A2 binding motif. These peptide candidates were screened first by their ability to be recognized by immunoglobulin G (IgG), and then by their ability to induce peptide-specific cytotoxic T lymphocytes (CTLs). As a result, five EZH2 peptides recognized by IgG (EZH2 120-128, EZH2 165-174, EZH2 569-577, EZH2 665-674, and EZH2 699-708) were frequently detected in the plasma of prostate cancer patients. Among them, the EZH2 120-128 and EZH2 165-174 peptides effectively induced HLA-A2-restricted and cancer-reactive CTLs from prostate cancer patients. The cytotoxicity was mainly dependent on EZH2 peptide-specific and HLA-A2-restricted CD8+ T cells. These results indicate that these EZH2 120-128 and EZH2 165-174 peptides could be promising candidates in peptide-based immunotherapy for HLA-A2+ prostate cancer patients.


Oligochitosan derivatives bearing electron-deficient aromatic rings for adsorption of amitriptyline: implications for drug detoxification.
The objective of this work is the synthesis of water-soluble oligochitosan derivatives with electron deficient aromatic rings for selective and rapid adsorption of amitriptyline through pi-pi complexation. Oligochitosan was chemically modified under homogeneous conditions in dimethyl sulfoxide (DMSO). (1)H NMR, FT-IR, and MALDI-TOF were employed in characterization, confirming that the electron deficient aromatic rings were chemically attached to the backbone of oligochitosan. Thromboelastography (TEG) revealed functionalized oligochitosan derivatives did not affect blood clotting. (1)H NMR was also utilized to observe the aromatic-aromatic interaction between electron deficient aromatic rings on oligochitosan and electron rich aromatic rings in amitriptyline. The chemical shift variation of aromatic protons in oligochitosan derivatives was followed to monitor the aromatic-aromatic interaction. Upfield shift of aromatic protons on benzenesulfonyl and dinitrobenzenesulfonyl groups was observed upon the addition of amitriptyline, supporting the formation of pi-pi complexes through aromatic-aromatic interactions. Dinitrobenzenesulfonyl rings show a larger variation in chemical shift due to the presence of the electron deficient nitro groups.


Barriers to shared decisions in the most serious of cancers: a qualitative study of patients with pancreatic cancer treated in the UK.
Less than 20% of patients with pancreatic cancer present with localized, potentially curable tumours. Even when potentially curative surgery is possible, mortality is high. Only 20-25% of patients who have had resected ductal adenocarcinoma of the pancreatic head survive 5 years. Other treatments include chemotherapy, radiotherapy and palliative care. To explore patients' perceptions of barriers to shared decision making in a condition in which shared decision making might be difficult. Thematic analysis of narrative interviews with 32 people diagnosed with pancreatic cancer in the UK; interviews with a social scientist, usually in people's homes. We found that barriers to shared decisions include the idea that investigations are conducted to determine whether the patient qualifies for surgery, rather than to establish whether surgery is an option to consider; a sense of being pressured to accept treatment, a sense that in a life-threatening situation, there are no 'real options'; and the confusion that can be caused when clinical opinions differ. We need to ask how patients can be expected to engage in an informed, shared decision if they are made to feel that they are one of the 'winners' if they qualify for surgery. When each treatment decision might have serious consequences for a patient's remaining months, we suggest that there is a particularly strong imperative to make sure that the patient is not subject to other people's assumptions about what is best for them and that patients are offered the opportunity to share in decisions.


Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood-brain barrier opening.
Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood-brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood-brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo.


ACCURACY OF ESTIMATED PHYLOGENIES: EFFECTS OF TREE TOPOLOGY AND EVOLUTIONARY MODEL.
A simulation study was carried out to investigate the relative importance of tree topology (both balance and stemminess), evolutionary rates (constant, varying among characters, and varying among lineages), and evolutionary models in determining the accuracy with which phylogenetic trees can be estimated. The three evolutionary context models were phyletic (characters can change at each simulated time step), speciational (changes are possible only at the time of speciation into two daughter lineages), and punctuational (changes occur at the time of speciation but only in one of the daughter lineages). UPGMA clustering and maximum parsimony ("Wagner trees") methods for estimating phylogenies were compared. All trees were based on eight recent OTUs. The three evolutionary context models were found to have the largest influence on accuracy of estimates by both methods. The next most important effect was that of the stemminess × context interaction. Maximum parsimony and UPGMA performed worst under the punctuational models. Under the phyletic model, trees with high stemminess values could be estimated more accurately and balanced trees were slightly easier to estimate than unbalanced ones. Overall, maximum parsimony yielded more accurate trees than UPGMA-but that was expected for these simulations since many more characters than OTUs were used. Our results suggest that the great majority of estimated phylogenetic trees are likely to be quite inaccurate; they underscore the inappropriateness of characterizing current phylogenetic methods as being for reconstruction rather than for estimation.


Conformational preferences and cis-trans isomerization of L-lactic acid residue.
The conformational study on N-acetyl- N'-methylamide of l-lactic acid (Ac-Lac-NHMe, the Lac dipeptide) is carried out using ab initio HF and density functional methods with the self-consistent reaction field method to explore its backbone conformational preferences and cis-trans isomerization for the depsipeptide with an ester bond in the gas phase and in solution. In the gas phase and in chloroform, the conformation tB with a trans depsipeptide bond is most preferred for the Lac dipeptide, whose backbone torsion angles are phi approximately -150 degrees and psi approximately -5 degrees , juxtaposed to those of the 3 10-helical structure. The larger shift in phi is brought to reduce the repulsion between the two carbonyl carbons of the acetyl and NHMe groups. However, the polyproline II-like tF conformation becomes more populated and the relative stability of conformation tB decreases significantly as the solvent polarity increases. This may be ascribed to weakening a C(5) hydrogen bond between the depsipeptidyl oxygen and the carboxyl amide hydrogen that plays a role in stabilizing the conformation tB in the gas phase and in chloroform. The cis populations about the depsipeptide bond are nearly negligible in the gas phase and in solution. The rotational barriers to the cis-trans isomerization of the depsipeptide bond for the Lac dipeptide are calculated to be about 11 kcal/mol, which is about half of those for the Ala dipeptide, although they increase somewhat with the increase of solvent polarity. The cis-trans isomerization of the depsipeptide bond proceeds through either clockwise or anticlockwise rotations with torsion angles of about +90 degrees or -90 degrees , respectively, in the gas phase and in solution, whereas it has been known that the isomerization proceeds through only the clockwise rotation for alanyl and prolyl peptide bonds. The pertinent distances between the depsipeptidyl oxygen and the carboxyl amide hydrogen can describe the role of this hydrogen bond in stabilizing the transition state structures in the gas phase and in solution.


AXIS: an instrument for imaging Compton radiographs using the Advanced Radiography Capability on the NIF.
Compton radiography is an important diagnostic for Inertial Confinement Fusion (ICF), as it provides a means to measure the density and asymmetries of the DT fuel in an ICF capsule near the time of peak compression. The AXIS instrument (ARC (Advanced Radiography Capability) X-ray Imaging System) is a gated detector in development for the National Ignition Facility (NIF), and will initially be capable of recording two Compton radiographs during a single NIF shot. The principal reason for the development of AXIS is the requirement for significantly improved detection quantum efficiency (DQE) at high x-ray energies. AXIS will be the detector for Compton radiography driven by the ARC laser, which will be used to produce Bremsstrahlung X-ray backlighter sources over the range of 50 keV-200 keV for this purpose. It is expected that AXIS will be capable of recording these high-energy x-rays with a DQE several times greater than other X-ray cameras at NIF, as well as providing a much larger field of view of the imploded capsule. AXIS will therefore provide an image with larger signal-to-noise that will allow the density and distribution of the compressed DT fuel to be measured with significantly greater accuracy as ICF experiments are tuned for ignition.


Older people's expectations regarding ageing, health-promoting behaviour and health status.
This paper is a study to explore the influence of expectations regarding ageing on physical and mental health status, and to examine the mediating effects of health-promoting behaviour on the relationship between these expectations and physical and mental health. To achieve healthy ageing, it is necessary for older people to play an active role in maintaining good health. Without any expectations for healthy ageing among older people themselves, encouraging them to participate in health-promoting behaviour and thereby to maintain good health would be unsuccessful. A convenience sample of 99 community-residing Korean older people was surveyed in 2007 via questionnaire using a short version of the Expectations Regarding Aging questionnaire, Health Promoting Lifestyle Profile II, and Medical Outcomes Study 12-item short form. Having a higher expectation about ageing was associated with better physical and mental health, after adjusting for age, gender and education. Expectations about ageing were partially mediated through the health-promoting behaviour that influenced physical and mental health. It may be necessary for nurses to make an effort to improve older people's expectations about ageing to help them achieve good health. Nursing interventions to improve these expectations need to be used in conjunction with an emphasis on older people's active involvement in health-promoting behaviour.


Lanthanum tetrazinc, LaZn4.
The structure of lanthanum tetrazinc, LaZn(4), has been determined from single-crystal X-ray diffraction data for the first time, approximately 70 years after its discovery. The compound exhibits a new structure type in the space group Cmcm, with one La atom and two Zn atoms occupying sites with m2m symmetry, and one Zn atom occupying a site with 2.. symmetry. The structure is closely related to the BaAl(4), La(3)Al(11), BaNi(2)Si(2) and CaCu(5) structure types, which can be presented as close-packed arrangements of 18-vertex clusters, in this case LaZn(18). The kindred structure types contain related 18-vertex clusters around atoms of the rare earth or alkaline earth metal.


High Mobility Group AT-Hook 2 (HMGA2) Oncogenicity in Mesenchymal and Epithelial Neoplasia.
High mobility group AT-hook 2 (HMGA2) has been associated with increased cell proliferation and cell cycle dysregulation, leading to the ontogeny of varied tumor types and their metastatic potentials, a frequently used index of disease prognosis. In this review, we deepen our understanding of HMGA2 pathogenicity by exploring the mechanisms by which HMGA2 misexpression and ectopic expression induces mesenchymal and epithelial tumorigenesis respectively and distinguish the pathogenesis of benign from malignant mesenchymal tumors. Importantly, we highlight the regulatory role of let-7 microRNA family of tumor suppressors in determining HMGA2 misexpression events leading to tumor pathogenesis and focused on possible mechanisms by which HMGA2 could propagate lymphangioleiomyomatosis (LAM), benign mesenchymal tumors of the lungs. Lastly, we discuss potential therapeutic strategies for epithelial and mesenchymal tumorigenesis based on targeting the HMGA2 signaling pathway.


Residual Block Based Nested U-Type Architecture for Multi-Modal Brain Tumor Image Segmentation.
Multi-modal magnetic resonance imaging (MRI) segmentation of brain tumors is a hot topic in brain tumor processing research in recent years, which can make full use of the feature information of different modalities in MRI images, so that tumors can be segmented more effectively. In this article, convolutional neural networks (CNN) is used as a tool to improve the efficiency and effectiveness of segmentation. Based on this, Dense-ResUNet, a multi-modal MRI image segmentation model for brain tumors is created. The Dense-ResUNet consists of a series of nested dense convolutional blocks and a U-Net shaped model with residual connections. The nested dense convolutional blocks can bridge the semantic disparity between the feature maps of the encoder and decoder before fusion and make full use of different levels of features. The residual blocks and skip connection can extract pixel information from the image and skip the link to solve the traditional deep traditional CNN network problem. The experiment results show that our Dense-ResUNet can effectively help to extract the brain tumor and has great clinical research and application value.


[Expression of PAPP-A, IGF-I and their effects on the cytological functions of siRNA lentiviral vector of hCASMCs IGF-I after inflammatory factor].
To evaluate expression of PAPP-A, IGF-I and the effect of TNF-alpha, IL-1beta on the cytological functions of hCASMCs with IGF-I gene silencing after inflammatory factor, in order to further study on the action of IGF axis hormone in the rupture of astable atheroxclerosis plaque. A RNA interference (RNAi) aimed at the gene of IGF-I was carried out to have an eukaryon transfection to hCASMCs. When the IGF- I-shRNA-hCASMC were treated by TNF-alpha, IL-1beta, IGFBP4, the expression of PAPP-A and IGF-I were detected with Western blot and ELISA. And then, the effect of TNF-alpha, IL-1beta, IGFBP4 on the proliferation of IGF-I-shRNA- hCASMC were assessed by MTT assay and changing in cell cycle and apoptosis were evaluated by using flow cytometry. Significant positive expression of PAPP-A in hCASMCs which were treated by TNF-alpha + IL-1beta or TNF-alpha + IL-1beta + IGFBP4 in Blank control (CON), Negative control (NC) and RNAi group were observed, but lower expression in the RNAi group than that in CON and NC groups. However, there was no positive expression of PAPP-A in hCASMCs of CON, NC, RNAi group treating without TNF-alpha + IL-1beta or TNF-alpha + IL-1beta + IGFBP4. The expression of IGF-I in hCASMCs of CON, NC, RNAi group treated with TNF-alpha + IL-1beta + IGFBP4 were greater than that only with or without TNF-alpha + IL-1beta treatment. In RNAi group, the A570 decreased when the hCASMCs treated with TNF-alpha + IL-1beta + IGFBP4 and significant lower than that in hCASMCs treated with TNF-alpha + IL-1beta. When the hCASMCs were treated with TNF-alpha + IL-1beta or TNF-alpha + IL-1beta + IGFBP4, the rate of apoptosis significantly increased in RNAi group, which was significantly higher than that in CON group and NC group. In addition, in RNAi group, the rate of apoptosis in hCASMCs treated with TNF-alpha + IL-1beta + IGFBP4 was significant higher than that in hCASMCs treated only with TNF-alpha + IL-1beta. When the IGF-I-shRNA-hCASMCs were stimulated by some inflammation factors, its proliferation decreased but the apoptosis enhanced. So the activated IGF-I level in local microebvironnment increased, which may cause the descend of cell proliferation and the increasing of apoptosis.


Immunohistochemical evidence of dysregulation of the mammalian target of rapamycin pathway in primary and metastatic pheochromocytomas.
To characterize the status of the mammalian target of rapamycin pathway using formalin-fixed, paraffin-embedded specimens from patients with primary and metastatic pheochromocytoma. Tissue microarrays were built from 19 normal adrenal medullas, 39 primary pheochromocytomas, and 8 unrelated metastatic pheochromocytomas. In 2 of the 8 cases of metastatic pheochromocytoma tissues, samples from the primary tumor were available. The expression levels of phosphatase and tensin homolog, phosphorylated Akt, phosphorylated S6, p27, and c-myc were evaluated by immunohistochemistry. The levels of phosphatase and tensin homolog and p27 were greater in the nontumor tissue than in the primary and metastatic pheochromocytomas. Increasing levels of phosphorylated Akt were noted in the nontumor adrenal medulla, primary pheochromocytomas, and metastatic pheochromocytomas. Finally, the levels of phosphorylated S6 were greater in the metastatic pheochromocytomas than in the nontumor adrenal medulla and primary pheochromocytomas. We found evidence of dysregulation of the mammalian target of rapamycin pathway in primary and metastatic pheochromocytomas, with increased phosphorylated S6 and phosphorylated Akt, and decreased phosphatase and tensin homolog and p27 expression levels. Because the currently available treatment modalities are less than optimal, our findings lend additional support to continuing to explore the utility of mammalian target of rapamycin pathway-targeted therapy for pheochromocytomas.


Novel nonpeptide CCK-B antagonists: design and development of quinazolinone derivatives as potent, selective, and orally active CCK-B antagonists.
We have designed a novel series of CCK-B receptor antagonists by combining key pharmacophores, an arylurea moiety of 1 and a quinazolinone ring of 3, from two known series. Our earlier studies showed that compounds with methylene linkers in our "target" produced moderate binding affinity and selectivity for CCK-B receptors, whereas its higher and lower homologues resulted in loss of affinity. Introduction of -NH- as a linker dramatically enhanced binding affinity and selectivity for CCK-B receptors, thus providing several compounds with single-digit nanomolar binding affinity and excellent selectivity. Analogous to the earlier studies of the series of quinazolinone derivatives 3, we also found 3-isopropoxyphenyl as a preferred substitution on the N-3 quinazolinone. Electron-withdrawing substitutions on the urea terminal phenyl ring enhanced the CCK-B potency. Representative compounds of this series were tested in the functional assay and showed pure antagonist profiles. Compounds 51 and 61 were orally active in the elevated rat X-maze test. These compounds were also evaluated for their pharmacokinetic profile. The absolute oral bioavailability of compound 61 was 22% in rats.


Simultaneous Measurement of the Galacturonate and Neutral Sugar Contents of Pectic Substances by an Enzymic-HPLC Method.
An enzymic-HPLC method was successfully applied to the simultaneous analysis of the galacturonate and neutral sugar contents of pectic substances. A mixture of seven neutral sugars that are present in oridnary pectins was eluted as one peak on a Shodex SUGAR SH1821 column, using 0.001 N sulfuric acid as the eluent; the peak was completely separated from that of galacturonate. No difference in the peak-area ratios of individual neutral sugars to glycerol (internal standard) was found among the seven; the relationship between the peak response and concentration was strictly linear throughout the entire concentration range studied. Seventeen pectic samples, including pectins, pectates, and rhamnogalacturonan fragments, were completely prehydrolyzed by Driselase, an industrial enzyme product from Irpex lacteus, and then analyzed for their constituent sugar contents. The enzymic-HPLC method was simple, accurate, and particularly useful for routine pectin analyses.


Oxygen consumption by rat lung after in vivo hyperoxia.
We studied the influence of 48 and 96 hours of in vivo hyperoxia (O2 greater than 98 per cent) on O2 consumption by rat lung slices. After 48 hours of hyperoxia, lung O2 consumption expressed per mg of deoxyribonucleic acid or per left lung decreased to approximately 70 per cent of that of lungs from rats exposed to compressed air. After 96 hours of hyperoxia, there was no difference in lung O2 consumption per mg of deoxyribonucleic acid between rats exposed to O2 and those exposed to air, but lung O2 consumption per left lung was higher in rats exposed to O2 than in those exposed to compressed air. Lung ribonucleic acid content and the ratio of ribonucleic acid to deoxyribonucleic acid were significantly increased after 96 hours of hyperoxia. We concluded that the rate of lung metabolism is altered after in vivo exposure to high PO2.


Transmitting Ainu traditional food knowledge from mothers to their daughters.
Since 2004, research has been conducted in the Ainu Indigenous community of the Saru River Region of Biratori in Northern Japan examining traditional food use knowledge. The purpose was to improve the socio-cultural environment for the Ainu People by implementing interventions meant to reintroduce traditional Ainu food use, so that they can live with dignity and in harmony with non-Ainu people in the heterogeneous community where Japanese cultural values dominate. Ten years after the start of this research, a series of interviews was conducted with Ainu mothers and daughters active in the community to evaluate the result of the interventions because, in accordance with culturally established Ainu gender roles, the Ainu women prepare the Ainu dishes. The interviews indicated that the community of both Ainu and non-Ainu people shared traditional Ainu food as a communal food at community events organized by the Ainu members of the community. The people in the community now identify traditional Ainu dishes with Ainu names, indicating the establishment of culinary and linguistic boundaries between Ainu traditional food and mainstream Japanese food. This also signals that the Ainu People have begun to establish a basis for reconstructing their unique ethnic identity, once suppressed by the government's former assimilation policy.


Early intervention and the role of pediatricians.
Growing evidence supports the efficacious nature of early intervention (EI) services to children with developmental delays and their families. Pediatricians can play a crucial role in identifying developmental delays and referring families to EI services provided by each state, under Part C of the Individuals with Disabilities Education Act (IDEA). The goals of this article are to educate pediatricians about the benefits of EI services and resources available within their state to help facilitate family involvement in EI. By being involved in the EI process, pediatricians can work as partners with parents and multidisciplinary teams to provide seamless coordinated care to children and their families.