Distinct pattern of lymphoid neoplasms characterizations according to the WHO classification (2016) and prevalence of associated Epstein-Barr virus infection in Nigeria population.
The present study aimed to classify lymphoid neoplasms according to the latest World Health Organization (WHO) classification and outlining the distribution in Nigeria of different entities. Additionally, the study describes the prevalence of lymphoid neoplasms associated with Epstein-Barr virus (EBV) infection in the Nigerian population. We collected 152 formalin-fixed paraffin-embedded (FFPE) tissues diagnosed as lymphoma from 2008 to 2018, coming from three different institutions located within three geopolitical zone in Nigeria. These institutions included the University College Hospital (UCH), Ibadan, Oyo State, the Enugu State University of Science and Technology Teaching Hospital (ESUTH), Enugu, Enugu State, and the Meena Histopathology and Cytology Laboratory (MHCL), Jos, Plateau State. From the total 152 cases retrieved, 50 were excluded due to insufficient tissue materials or inconclusive antigen reactivity. We confirmed 66 (64.7%) cases as lymphomas out of the remaining 102 FFPE with a male to female ratio of 2:1 and a mean age of 44.4 years. Ten entities were identified, and of these, chronic lymphocytic leukemia (CLL) was the most prevalent category (34.8%). For the diffuse large B-cell lymphomas not otherwise specified (DLBCL, NOS), the germinal centre B-cell type was the most common (71.4%). Ten lymphoma cases (15.2%) were positive for Epstein-Barr virus (EBV), most of which were Hodgkin lymphoma (HL). CLL was common in the Hausa ethnic group, HL in the Yoruba ethnic group, while the Igbo ethnic group had an equal distribution of CLL, HL, and DLBCL diagnosis. Although the distribution of lymphomas in Nigeria shares some similarities with those of other countries, we described distinct features of some subtypes of lymphomas. Also, the study underscores the need for a more precise diagnosis and classification of lymphoid neoplasms in Nigeria using the latest WHO classification.


The utility of therapeutic hypothermia on cerebral autoregulation.
Cerebral autoregulation (CA) dysfunction is a strong predictor of clinical outcome in patients with acute brain injury (ABI). CA dysfunction is a potential pathologic defect that may lead to secondary injury and worse functional outcomes. Early therapeutic hypothermia (TH) in patients with ABI is controversial. Many factors, including patient selection, timing, treatment depth, duration, and rewarming strategy, impact its clinical efficacy. Therefore, optimizing the benefit of TH is an important issue. This paper reviews the state of current research on the impact of TH on CA function, which may provide the basis and direction for CA-oriented target temperature management.


Association Between Travel Distance and Use of Postoperative Radiation Therapy Among Men With Organ-Confined Prostate Cancer: Does Geography Influence Treatment Decisions?
After radical prostatectomy, men with adverse pathologic features or a persistent postoperative detectable prostate-specific antigen (PSA) are candidates for postoperative radiation therapy (PORT). Previous data have suggested disparities in receipt of adjuvant radiation therapy for adverse pathologic features according to travel distance. Among patients without adverse pathologic features (pT2 disease and negative margins), the main indication for PORT is a persistent postoperative detectable PSA. However, it remains unknown whether the rate of receipt of PORT in this cohort of men with persistently detectable PSA is related to travel distance from the treating facility. Using the National Cancer Database, we identified 170,379 men with prostate cancer diagnosed from 2004 to 2015 managed with upfront surgery who were found to have pT2 disease with negative surgical margins. Multivariable logistic regression defined adjusted odds ratios (AORs) with 95% confidence intervals (CIs) of receiving PORT as the primary dependent variable and distance (<5, 5-10, 10-20, ≥20 miles from the treatment facility) as the primary independent variable. Within our cohort, progressively farther distance from the treatment facility was associated with lower rates of PORT. In patients living <5 miles, 5 to 10 miles, 10 to 20 miles, and >20 miles from the treating facility, rates of PORT of were 1.37% (referent), 1.16% (AOR, 0.90; 95% CI, 0.79-1.04; P = .158), 0.98% (AOR, 0.80; 95% CI, 0.70-0.93; P = .003), and 0.64% (AOR, 0.47; 95% CI, 0.41-0.54; P < .001), respectively. For men with localized prostate cancer without adverse pathologic features managed with surgery, increasing distance from treatment facility was associated with lower receipt of PORT. Given that the rate of a persistent postoperative detectable PSA is unlikely to depend on the distance to the treatment facility, these findings raise the possibility that the geographic availability of radiation treatment facilities influences the decision to undergo PORT for patients with persistent postoperative detectable PSA.


Bexarotene--an alternative therapy for progressive cutaneous T-cell lymphoma? First experiences.
A standard therapy for advanced cutaneous T-cell lymphomas has not yet been defined. Bexarotene is a new retinoid x receptor-specific retinoid that has been approved for systemic second-line therapy for cutaneous T-cell lymphomas in the USA and Europe. In order to evaluate the efficacy of bexarotene in cutaneous T-cell lymphomas, a pilot trial was initiated. In a pilot project 10 patients with advanced cutaneous T-cell lymphomas, who had received a variety of previous treatments, were treated with bexarotene at the departments of dermatology in Münster, Minden and Charité Berlin, Germany. The patients received bexarotene at a dose of 300 mg/m2 body surface daily. According to the percentage of tumour reduction and affected body surface, the response rates were divided in complete and partial remission, stable disease and progressive disease. Laboratory parameters i.e. cholesterol, triglycerides transaminases, T3, T4, and TSH were screened regularly. In 2 patients a short partial remission was achieved; however, after a few weeks progression followed. In 4 patients a lasting stabilisation was obtained. The other 4 patients showed a progressive disease during therapy. 6 patients developed hypertriglyceridemia with levels up to 2000 mg/dl; therapy had to be suspended in 3 patients because of these adverse drug events. Weighing benefits and risks, bexarotene can at present not be recommended as standard therapy in the treatment of patients with progressive cutaneous lymphomas.


Intranasal immunization using biphasic lipid vesicles as delivery systems for OmlA bacterial protein antigen and CpG oligonucleotides adjuvant in a mouse model.
The nasal mucosa is an important arm of the mucosal system since it is often the first point of contact for inhaled antigens. The ineffectiveness of the simple delivery of soluble antigens to mucosal membranes for immunization has stimulated extensive studies in appropriate delivery systems and adjuvants. We have evaluated biphasic lipid vesicles as a novel intranasal (i.n.) delivery system (designated as vaccine targeting adjuvant, VTA) containing bacterial antigens and CpG oligodeoxynucleotides (ODNs). Results show that administration of antigen and CpG ODNs in biphasic lipid vesicles resulted in greater induction of IgA levels in serum (P< 0.05) and mucosal antibody responses such as IgA in nasal secretions and lung (P< 0.01) after immunization with a combined subcutaneous (s.c.)/i.n. as compared to s.c./s.c. approach. Based on antibody responses, VTA formulations were found to be suitable as delivery systems for antigens and CpG ODNs by the intranasal route, resulting in a Th2-type of immune response, characterized by IgG1 and IL-4 production at the systemic level.


Strengthening the scientific record.
Science is a social process. Discoveries-even by supposed "lone" geniuses-do not become knowledge until the findings are shared with the scientific community, to be vetted, challenged, and expanded on. Since the birth of the digital age, this discourse has become much more apparent, as communication outlets such as social media, blogs, and websites such as PubPeer and Retraction Watch allow the scientific community to discuss new findings. Further, the availability of greater amounts of data that support findings allows peers to redo key analyses to confirm or report discrepancies. This week, Science is announcing two changes-one to accelerate the conversation about papers and another to ease deposition of supporting data-that will facilitate the evaluation of research findings across the wide scientific enterprise.


Sleep-dependent hyperprolactinemia and Corpus luteum pathogenesis.
The results obtained in wake and sleep conditions by PRL determinations performed in 6 normoprolactinemic infertile women with luteal phase deficiency (LPD) are reported. Infertility was apparently due to LPD. PRL levels were determined by RIA in blood samples collected at 20-min intervals from 18(00) to 08(00). LPD has been previously demonstrated by endometrial biopsy, basal temperature and circulating progesterone determinations. PRL levels were also determined in 5 normal women used as control subjects under the same experimental conditions. The results obtained, expressed as means +/- SD of LPD vs. control group, were 15.9 +/- 4.6 vs. 11.6 +/- 3.3 ng/ml (p greater than 0.1) in wake conditions and 31.9 +/- 5.9 vs. 21.4 +/- 5.7 ng/ml (p less than 0.01) in sleep conditions. PRL values during the highest pulse (HP) in sleep and wake conditions were 20.9 +/- 5.2 vs. 17.0 +/- 3.3 ng/ml (p less than 0.1) and 51.1 +/- 17.1 vs. 34.3 +/- 2.4 ng/ml (p less than 0.01), respectively. In 2 out of the 6 patients mean PRL values were 22.0 and 26.5 ng/ml during sleep, and 26.0 and 33.0 ng/ml during HP. These values were not statistically significant when compared with those obtained in the control group. The results obtained show that 4 out of the 6 patients with LPD and normal PRL levels in wake conditions had sleep-dependent hyperprolactinemia due to the pulses with a more significant amplitude. These findings suggest that in some cases sleep-induced hyperprolactinemia might be involved in LPD pathogenesis.


Demineralized bone matrix and spinal arthrodesis.
Spinal fusion is a gold-standard treatment for many disorders of the spine with autogenous bone graft as the gold-standard source for augmenting fusion. However, the morbidity and limitations of autogenous bone grafting has motivated the search for bone graft alternatives. One such alternative is demineralized bone matrix (DBM). The purpose of this paper is to describe and characterize the properties of DBM in addition to reviewing the results of its use in animal and human studies of spinal fusion. A thorough and critical review of the English-language literature was conducted. DBM is both osteoconductive and osteoinductive. Studies have produced variable results with respect to spinal fusion rates. Various studies have demonstrated inferior, equal, or enhanced fusion rates. Some of the differences in these studies include the animal models used, the manner in which DBM was prepared, and the carrier with which DBM was combined. These differences may account for the dissimilar results. DBM is able to function as a graft extender in the human species.


Pain relief after arthroscopic surgery of the knee: a prospective, randomized, and blinded assessment of bupivacaine and bupivacaine with adrenaline.
A prospective, randomized, and double-blind study was conducted to compare the influence on postoperative pain of equal volumes of saline, bupivacaine, or bupivacaine with adrenaline, injected both intraarticularly and into the wound puncture site, for 118 day case patients undergoing elective knee arthroscopy. Marginal analyses of postoperative visual analogue pain scores and postoperative fentanyl doses showed that the group given bupivacaine with adrenaline had less postoperative pain when compared with the saline group. However, when multifactor analyses were performed, preoperative visual analogue pain scores, operation type and length, and the sex of the patient were all shown to be significant predictors of postoperative pain, but the use of bupivacaine was not. We conclude that the observed differences in postoperative pain were due to differences between the groups in these predictive factors, especially preoperative pain scores, and that the use of bupivacaine was less important and not statistically significant in influencing postoperative pain.


Triclosan induces immunosuppression and reduces survivability of striped catfish Pangasianodon hypophthalmus during the challenge to a fish pathogenic bacterium Edwardsiella tarda.
Toxicological studies on the emergent pollutant, triclosan (TCS) have established the wide-ranging effects of the compound on fish and other aquatic organisms. Although the available literature describes the standalone effects of TCS on growth and metabolism of fish yet, reports about the combined effects of TCS with microbial pathogens are scarce. In a real environment, a combined exposure to TCS and pathogens is of common occurrence, therefore, such investigation facilitates in developing a better understanding about the gross effects of pollutants and microbial pathogens on aquatic organisms including fish. In this context, the experimental fish (striped catfish, Pangasianodon hypophthalmus) were exposed to three different concentrations of TCS viz. 10, 20 and 30% of 96 h LC50 (1177 μg L-1) for 45 days including two control group firstly solvent control (without TCS) group and another one (without solvent and TCS) group in triplicate. Sampling was performed fortnightly and blood, serum and tissues (liver, and gills) samples were collected for evaluating immunological and biochemical parameters. Following 45 days of the experiments, the experimental fish in each treatment group including controls were challenged with a fish pathogenic bacterium Edwardsiella tarda (LD50 dose) and fish mortality was daily monitored for calculating cumulative mortality till 7 days and further, relative per cent survivable was estimated. A significant reduction in cellular immune responses i.e. respiratory burst activity (RBA), myeloperoxidase activity (MPO), phagocytic activity (PA) and humoral immune components viz. serum lysozyme activity, total immunoglobulin in serum, ceruloplasmin level, serum total protein, albumin and globulin level was evident in TCS exposed groups in comparison to control during the experimental periods. Further, oxidative stress parameters viz. superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST) activity in liver and gill tissue exhibited a dose-dependent increase in activity with related to TCS concentration during the experimental periods. A significant reduction in relative percentage survival was observed with increasing TCS concentration. The present study reveals that TCS can inhibit the cellular and humoral components of the innate immune system of the fish and can elevate the mortality due to TCS mediated immunosuppression in fish during the bacterial infection.


Sustained remission of an extensive monoclonal, Epstein-Barr virus-associated diffuse large B cell lymphoma in a kidney-pancreas transplant recipient.
Epstein-Barr virus associated posttransplant high-grade large cell lymphoma (EBV-PTL) is thought to be incurable solely by cessation of immunosuppression. We report a case of EBV-PTL resolving rapidly after alleviation of immunosuppression. A strong cytotoxic memory T cell (CTL) reaction against two individual recipient EBV strains appears to be involved. EBV strain identification in donor lymphocytes, tumor cells of EBV-PTL, and circulating lymphocytes of recipient was performed by latent membrane protein 1 fingerprinting. Stage IIIB EBV-PTL of recipient type was cured through strong autologous CTL reaction consecutive to alleviation of immunosuppression. Latent membrane protein 1 fingerprinting identified three different EBV strains; namely in lymphoma and peripheral lymphocytes of donor and recipient. In the setting of solid organ transplantation, rigorous reduction of immunosuppression may lead to cure of high grade EBV-PTL, if the recipient delivers a strong host CTL reaction against the epitopes of EBV latency gene products. Infection with two individual EBV strains earlier in life may increase the number of specific CTL clones and increase the memory capacity.


Yttrium-90 radioembolization in desmoplastic small round cell tumor with recurrent hepatic metastasis following hyperthermic intraperitoneal chemotherapy.
We report a case of a 26-year-old male who was diagnosed with metastatic desmoplastic small round cell tumor initially treated with systemic chemotherapy followed by tumor debulking and hyperthermic intra-peritoneal chemotherapy. The patient was in complete remission by clinical and imaging criteria for 11 months, until he developed bi-lobar hepatic disease, which was successfully treated with selective internal radiation therapy by Yttrium-90. The patient demonstrated liver-specific complete response on follow-up imaging obtained 18 months after the procedure.


Cost-effectiveness analysis of ovarian tissue cryopreservation and transplantation for preservation of fertility in post-pubertal oncological women submitted to high-risk gonadotoxic chemotherapy.
To study the economic impact of ovarian tissue cryopreservation and transplantation (OTC) in post-pubertal patients who underwent high-risk gonadotoxic chemotherapy. A decision tree model was used to determine the live birth rate and cost-effectiveness of OTC versus non-OTC. The incremental cost-effectiveness ratio (ICER) was calculated. A sensitivity analysis was performed under the assumption that the costs of ovarian cortex retrieval, cryopreservation, and storage for patients with cancer might be covered by the national health system or health insurance. Patients had the greatest probability of achieving live birth after high-risk chemotherapy when they underwent OTC versus non-OTC. Although cryopreservation of ovarian tissue results in higher live birth rates, it is always more expensive. Cost-effectiveness increases when the majority of patients completes the path of tissue cryopreservation plus transplantation after 5 years. Although OCT has been demonstrated as a procedure for effective fertility preservation in fertility-age women with cancer, no cost-effectiveness analysis has been performed until now. This model could help healthcare systems to allocate coverage for OCT.


Japan's Advocacy for Human Security in Global Politics: Case Study of Japan's Grant Assistance for Grass-Roots Human Security Projects (GGP) in the State of Sabah, Malaysia, 2000-2021.
After World War II, Japan became a major recipient of foreign aid from the USA. As Japan's economy improved in the 1960s, it played a significant role as a global aid donor in world politics through its Official Development Assistance (ODA). This commitment continued into the 1990s when Japan, as one of the leading proponents of the concept of human security, began providing humanitarian aid to more countries across the globe. To better understand the notion of human security in international politics, this paper examines Japan's endorsement of the concept in its foreign policy strategy. This paper provides an overview and critical assessment of Japan's Grant Assistance for Grass-Roots Human Security Projects (GGP) in the state of Sabah in East Malaysia from 2000 to 2021. This paper argues that different contexts and circumstances in the state of Sabah require further study, especially for understanding Japan's focus and concern in the area of basic human security needs, as enshrined in the GGP philosophy. Despite Japan's GGP objective as part of its foreign policy to promote human development, the execution of its foreign aid in Sabah does have issues. This paper concludes that the implementation of Japan's GGP necessitates greater inclusion, particularly for other vulnerable groups and underdeveloped areas in Sabah. Despite Japan's GGP objective as part of its foreign policy to promote human development, the execution of its foreign aid in Sabah does have issues. This paper concludes that the implementation of Japan's GGP necessitates greater inclusion, particularly for other vulnerable groups and underdeveloped areas in Sabah.


Advances in diagnosis of chronic liver diseases in pediatric patients.
Chronic liver diseases (CLD) present important clinical problem in children with various age-dependent causes. Nonalcoholic fatty liver disease (NAFLD) with its increasing prevalence is a major problem with regard to its timely recognition and the need for long-term disease monitoring. At present, a perfect non-invasive method for the evaluation of liver fibrosis is not available. A non-systematic literature search was performed to summarize the current knowledge about transient elastography (TE) with controlled attenuation parameter (CAP) in children with CLD. Ovid MEDLINE, Ovid EMBASE, Google scholar, and The Cochrane Library databases were searched for relevant articles evaluating TE in the pediatric population. Normal values of liver stiffness measurements (LSM) according to the age are given, as well as the advantages and disadvantages of the method. The utility of TE in specific liver disease in pediatric population is summarized. TE with CAP is a valuable non-invasive method for the liver-damage assessment. Clinical interpretation of TE results should be made in parallel with the assessment of the patient's demographics, disease etiology, and essential laboratory parameters.


Agonist-induced alteration in the membrane form of muscarinic cholinergic receptors.
Incubation of 1321N1 human astrocytoma cells with carbachol resulted in a rapid loss of binding of [3H]N-methylscopolamine ([3H]NMS) to muscarinic cholinergic receptors measured at 4 degrees C on intact cells; loss of muscarinic receptors in lysates from the same cells measured with [3H]quinuclidinyl benzilate [( 3H]QNB) at 37 degrees C occurred at a slower rate. Upon removal of agonist from the medium, the lost [3H]NMS binding sites measured on intact cells recovered with a t1/2 of approximately 20 min, but only to the level to which [3H]QNB binding sites had been lost; no recovery of "lost" [3H]QNB binding sites occurred over the same period. Based on these data and the arguments of Galper et al. (Galper, J. B., Dziekan, L. C., O'Hara, D. S., and Smith, T. W. (1982) J. Biol. Chem. 257, 10344-10356) regarding the relative hydrophilicity of [3H]NMS versus [3H]QNB, it is proposed that carbachol induces a rapid sequestration of muscarinic receptors that is followed by a loss of these receptors from the cell. These carbachol-induced changes are accompanied by a change in the membrane form of the muscarinic receptor. Although essentially all of the muscarinic receptors from control cells co-purified with the plasma membrane fraction on sucrose density gradients, 20-35% of the muscarinic receptors from cells treated for 30 min with 100 microM carbachol migrated to a much lower sucrose density. This conversion of muscarinic receptors to a "light vesicle" form occurred with a t1/2 approximately 10 min, and reversed with a t1/2 approximately 20 min. In contrast to previous results in this cell line regarding beta-adrenergic receptors (Harden, T. K., Cotton, C. U., Waldo, G. L., Lutton, J. K., and Perkins, J. P. (1980) Science 210, 441-443), agonist binding to muscarinic receptors in the light vesicle fraction obtained from carbachol-treated cells was still regulated by GTP. One interpretation of these data is that agonists induce an internalization of muscarinic receptors with the retention of their functional interaction with a guanine nucleotide regulatory protein.


Candidate pathway association study in cocaine dependence: the control of neurotransmitter release.
Cocaine is the second most used illegal drug in Europe. The transition from use to dependence involves both genetic and environmental factors. Genetic variation in neurotransmitter systems is involved in the susceptibility to cocaine dependence. We examined the possible contribution to cocaine dependence of 16 genes involved in the cellular machinery that controls neurotransmitter release: genes encoding proteins of the SNARE complex (STX1A, SNAP25, VAMP1 and VAMP2), fusion control elements (SYT1, SYT2, CPLX1, CPLX2, CPLX3 and CPLX4) and regulatory elements (STXBP1, SYP, SNPH, NSF, NAPA and RAB3A). We genotyped 121 SNPs, selected according to genetic coverage criteria, in 360 cocaine-dependent patients and 360 controls from Spain. Single and multiple-marker analyses revealed a strong association between cocaine dependence and the NSF gene, encoding the N-ethylmaleimide-sensitive factor (P = 5.1e-04, OR = 2.44 (1.45-4.00) and P = 0.001, OR = 1.82 (1.28-2.59), respectively). The presence and absence of psychotic symptoms were also studied. Interestingly, when we considered the time between initial consumption and the onset of cocaine dependence, we observed that the association was mainly restricted to the group of patients that rapidly developed drug dependence (≤ 2 years; P = 2.98e-06, OR = 1.33 (1.20-1.47)). Our data show preliminary evidence that NSF may predispose not only to cocaine dependence, but also to an early onset of the dependence.


Hearing impairment and associated morphological changes in pituitary adenylate cyclase activating polypeptide (PACAP)-deficient mice.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a regulatory and cytoprotective neuropeptide, its deficiency implies accelerated aging in mice. It is present in the auditory system having antiapoptotic effects. Expression of Ca2+-binding proteins and its PAC1 receptor differs in the inner ear of PACAP-deficient (KO) and wild-type (WT) mice. Our aim was to elucidate the functional role of PACAP in the auditory system. Auditory brainstem response (ABR) tests found higher hearing thresholds in KO mice at click and low frequency burst stimuli. Hearing impairment at higher frequencies showed as reduced ABR wave amplitudes and latencies in KO animals. Increase in neuronal activity, demonstrated by c-Fos immunolabeling, was lower in KO mice after noise exposure in the ventral and dorsal cochlear nuclei. Noise induced neuronal activation was similar in further relay nuclei of the auditory pathway of WT and KO mice. Based on the similar inflammatory and angiogenic protein profile data from cochlear duct lysates, neither inflammation nor disturbed angiogenesis, as potential pathological components in sensorineural hearing losses, seem to be involved in the pathomechanism of the presented functional and morphological changes in PACAP KO mice. The hearing impairment is probably concomitant with the markedly accelerated aging processes in these animals.


The Italian National Food Consumption Survey INRAN-SCAI 2005-06: main results in terms of food consumption.
The current paper aims to present the main results of the Italian National Food Consumption Survey INRAN-SCAI 2005-06. A cross-sectional study was performed. Households were randomly selected after geographical stratification of the national territory. Food consumption was assessed on three consecutive days through individual estimated dietary records. Italy. The final study sample comprised 3323 subjects (1501 males and 1822 females) aged 0.1 to 97.7 years belonging to 1329 households: fifty-two infants (0-2.9 years), 193 children (3-9.9 years), 247 teenagers (10-17.9 years), 2313 adults (18-64.9 years) and 518 elderly (65 years and above). Participation rate was 33 %. The mean ratio of estimated energy intake to estimated BMR was 1.41 in adults. Indicators of mean and high individual consumption are presented for fifteen large categories and fifty-one subcategories of foods and beverages, in the total population and in consumers, by age and sex categories. The overall consumption of fruit and vegetables was 418 g/d. The consumption of red meat was approximately 700 g/week, expressed as raw weight. Some specific aspects of the Italian food consumption pattern were confirmed: a large contribution from bread, pasta and pizza to cereals, from olive oil to fats and from wine to alcoholic beverages. The database obtained from the survey will be the key reference for Italian food consumption during the coming years and will be utilized for a variety of purposes including the assessment of nutrient intakes and risk analysis.


Rare gastric neoplasm: Malignant glomus tumor of the stomach. A case report.
Glomus tumors are rare neoplasms that aris-e from neuromyoarterial canal or glomus body. They are mainly found in the peripheral soft tissue, extremities and rarely developed inside the gastrointestinal tract. In the gastrointestinal tract, the stomach is the most common site for the development of glomus tumors, and most often found in the antrum. Usually, the symptoms of gastric glomus tumors are non specific i.e (abdominal pain, GI bleeding and/or perforation) and possibly discovered incidentally during upper GI endoscopy. This is a-56-year-old-male, presented to the emergency department with upper GI bleeding i.e (melena), and signs of shock (HR: 110; BP:80/60), Blood tests showed Hemoglobin level: 5 g/dl. Resuscitation was started with IV fluid and transfusion of 4 units of PRBCs. After resuscitation, He gave a 10 days history of passing black tarry stool, palpitation, headache, dizziness, easily fatigability, malaise, and colicky epigastric abdominal pain. His abdomen was soft, lax with no tenderness, there was fullness at the left upper quadrant. Upper GI endoscopy was performed that showed a large gastric ulcer with adherent clots, necrotic base and oozing at the proximal part of the greater curvature, after that the bleeding was managed with a heater probe and epinephrine injections. The histopathological examination of the biopsy revealed a spindle and epithelioid tumor with the top differential diagnosis being GIST, however other submucosal lesions cannot be excluded. After that, He underwent exploratory laparotomy and wedge resection of the tumor. The final histopathology showed a malignant glomus tumor. Due to overlapping clinical and radiological features between glomus, GIST and other submucosal lesions, the histopathological examination is considered to be the gold standard for the diagnosis. Surgical resection with negative margin is the treatment of choice for gastric glomus tumors. Although gastric glomus tumor is a rare entity and accounts for 1% of all gastric mesenchymal tumors, it should be considered in the differential diagnosis, since preoperative biopsy is difficult and overlapping features with other submucosal lesions. Surgical treatment is the preferred option for gastric glomus tumor and long-term follow-up is required due to high metastatic and recurrence rate in the malignant type.


Sex steroid hormones, leptin, and high-sensitivity C-reactive protein levels in adolescents.
The association of sex hormones with C-reactive protein (CRP) levels has been reported. However, this association remains unexplored in children in whom important anthropometric and hormonal changes are taking place. To analyze the association between high-sensitivity CRP (hs-CRP) and testosterone, estradiol and sex hormone-binding globulin (SHBG) levels in a population-based sample of adolescents, and to evaluate the influence of leptin levels on this association. The sample population of this cross-sectional study was comprised of 338 male and 385 female adolescents, aged 12-16 years. Information on anthropometric variables, hormone, leptin, and hs-CRP levels was available. In male adolescents in our study, higher age is significantly associated with higher testosterone levels and with lower leptin and SHBG concentrations across the range of age studied. No significant changes in leptin and SHBG levels by age are observed in females. In males, leptin correlates negatively with testosterone levels (-0.263, p < 0.001), showing a stronger correlation after adjusting by body mass index (BMI) (-0.424, p < 0.001). A significant correlation between hs-CRP and testosterone levels is observed in males after adjusting by BMI, but the correlation disappears after adjusting by leptin. No association between testosterone and hs-CRP was observed in females. The negative association between hs-CRP levels and SHBG remains significant after adjusting by leptin in both sexes but disappears in males after adjusting by BMI. The negative association between hs-CRP and testosterone concentrations observed in 12- to 16-year-old males seems to be related to leptin levels which are closely negatively related to testosterone levels in males independently of BMI.


The immunogenic effect of purified antigens of B. alexandrina against S. mansoni in experimental animals (II) as measured by the histopathological changes in the liver.
It can be safely said that up till now, no method of vaccination (including recent genes encoding vaccines) has yet proved to be totally effective since they gave partial and low levels of protection against S. mansoni infection. The objective of this work is to try testing the immunogenic effect of two purified non infected B. alexandrina hepatopancreas through histopathological changes in liver of Swiss albino mice (15-20 gm). Gel filtration chromatography was used to fractionate the crude antigen into five fractions followed by re-fractionation and determination of their molecular weights by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Four dilutions of Fiv (20000-29000 daltons) and Fv (20000-24000 daltons) were injected in two groups of mice (33 each) at weekly intervals and another control group was injected with phosphate buffer saline (PBS) in the same manner. Sacrification was done seven weeks from infection with 100 S. mansoni cercariae through immersion method. The results revealed that there is marked histopathological changes in liver of the control group in comparison to the two vaccinated groups which appear more or less normal with slight inflammatory infiltrate.


Endoscopic findings and outcomes of revisional procedures for patients with weight recidivism after gastric bypass.
Significant weight regain occurs for 10% to 20% of patients after Roux-en-Y gastric bypass (RYGB). Potential causative factors include anatomic abnormalities such as enlargement of the gastric pouch and gastrojejunostomy (GJ). This report describes endoscopic findings for patients referred for investigation of weight regain and presents the outcomes of revisional therapy for patients with abnormal anatomy. To evaluate gastric pouch and stoma size, RYGB patients referred for weight regain underwent upper endoscopy. A GJ was defined as enlarged if it had a diameter greater than 2 cm in any dimension, and a pouch was defined as enlarged if its length exceeded 6 cm long or its width exceeded 5 cm. Patients with abnormal anatomy who subsequently underwent revisional procedures were arbitrarily categorized into three groups based on the interval from RYGB to endoscopic evaluation: less than 5 years (group 1), 5 to 10 years (group 2), longer than 10 years (group 3). The percentage of regained weight lost (%RWL) after revision was compared between the groups. In this study, 205 RYGB patients (176 women with a mean age of 47 ± 10 years and a current body mass index [BMI] of 43.4 ± 8.4 kg/m(2)) were evaluated. The mean time from primary RYGB was 6.9 ± 3.7 years, and the increase in BMI from its nadir was 9.78 ± 5.80 kg/m(2). Abnormal endoscopic findings (n = 146, 71.2%) included large GJ (n = 86, 58.9%), large pouch (n = 42, 28.8%), or both (n = 18, 12.3%). Of the 205 patients, 51 (24.9%) underwent a revisional surgical or endoluminal procedure. At a mean follow-up assessment 13 months after revision, group 1 (n = 12) had a mean %RWL of 103% ± 89.3%, and 62% of these patients lost all their regained weight. The mean %RWL was 45% ± 12.6% in group 2 (n = 30) and 40% ± 13.6% in group 3 (n = 9). Endoscopy is a valuable tool for evaluating weight regain after bariatric surgery that can identify abnormal post-RYGB anatomy in a majority of patients. Revisional procedures to restore normal RYGB anatomy appear to be most successful if performed within 5 years after the primary procedure.


Insulin pump dosing across gestation in women with well-controlled type 1 diabetes mellitus.
We hypothesized that bolus and basal insulin doses in women with type 1 diabetes mellitus who use insulin pumps would increase 2-fold to maintain hemoglobin A1c <6.5% across gestation. This was a retrospective study of 9 women with type 1 diabetes mellitus with preconceptional hemoglobin A1c ≤ 7.4% using insulin pumps. The primary outcome was absolute and percentage change of basal and bolus insulin from preconception to delivery. Total daily dose of insulin increased from 33.3 ± 7.8 U/d before conception to 93.5 ± 27.9 U/d at delivery. Basal rates rose modestly (50% increase, from 16.2 ± 6.5 U/d to 24.0 ± 9 U/d); bolus insulin doses quadrupled from 17.1 ± 6.1 U/d to 69.5 ± 29.6 U/d (P = .0001). Bolus insulin increased from approximately 50% of total daily dose of insulin before conception to 75% of total daily dose of insulin at 36 weeks' gestation. In well-controlled type 1 diabetes mellitus, insulin requirements increased 3-fold from before conception to 36 weeks' gestation. Most of this requirement was attributed to an increase in bolus rates that are required for control with meals.


Use of artificial intelligence to identify data elements for The Japanese Orthopaedic Association National Registry from operative records.
The Japanese Orthopaedic Association National Registry (JOANR) was recently launched in Japan and is expected to improve the quality of medical care. However, surgeons must register ten detailed features for total hip arthroplasty, which is labor intensive. One possible solution is to use a system that automatically extracts information about the surgeries. Although it is not easy to extract features from an operative record consisting of free-text data, natural language processing has been used to extract features from operative records. This study aimed to evaluate the best natural language processing method for building a system that automatically detects some elements in the JOANR from the operative records of total hip arthroplasty. We obtained operative records of total hip arthroplasty (n = 2574) in three hospitals and targeted two items: surgical approach and fixation technique. We compared the accuracy of three natural language processing methods: rule-based algorithms, machine learning, and bidirectional encoder representations from transformers (BERT). In the surgical approach task, the accuracy of BERT was superior to that of the rule-based algorithm (99.6% vs. 93.6%, p < 0.001), comparable to machine learning. In the fixation technique task, the accuracy of BERT was superior to the rule-based algorithm and machine learning (96% vs. 74%, p < 0.0001 and 94%, p = 0.0004). BERT is the most appropriate method for building a system that automatically detects the surgical approach and fixation technique.


Recent developments in chromatographic purification of biopharmaceuticals.
Over the last several decades, researchers have time and again proposed use of non-chromatographic methods for processing of biotherapeutic products. However, chromatography continues to be the backbone of downstream processing, particularly at process scale. There are many reasons for this, critical ones being the unparalleled scalability, robustness, and selectivity that process chromatography offers over its peers. It is no surprise then that process chromatography has been a topic of major developments in resin matrix, ligand chemistry, modalities, high throughput process development, process modelling, and approaches for control. In this review, we attempt to summarize major developments in the above-mentioned areas. Greater significance has been given to advancements in the last 5 years (2013-2017).


[Evaluation of carboxy-angiography in the study of arteriopathy of the lower limbs].
We prospectively compared the safety and the usefulness of CO2 with iodinated contrast material in the study of lower limb arteries. The study included 30 patients (20 men, 10 women, mean age 67) suffering from lower limb ischemia: stage II (3), stage III (13), stage IV (9), Leriche syndrome (1), post-operative (4). We systemically performed an aortic injection (L3), via a 4F catheter, of (1) CO2-DSA (5 to 6 injections of 75 ml at a flow rate of 20 ml/s) and (2) DSA with iodine contrast material (100 ml at a flow rate of 8 ml/s). Patients were monitored for pain and vital signs. Four reviewers did a subjective evaluation of the vessel visibility at five levels (pelvis, thigh, knee, calf, ankle). No side effect was found. Concerning pain, the patients had the same sensation in 53%; pain was more disagreeable with CO2 in 40%, more disagreeable with iodine in 7%. Concerning vessel visualization, there was a good coherence between the readers and we found the same quality in 61%. CO2 was less informative in 35%, and more informative in 4%. Image quality decreased with fragmentation of the gas and remoteness of injection site. CO2 angiography, with electronic injection, is a safe alternative to conventional angiography with iodinated contrast material. The disagreeable sensations can be reduced with explanations given before injection and reducing flow rate. Image stacking software could imitate the side effects of fragmentation of the CO2 bubble. This method appears to be a good alternative for patients with severe renal impairment or allergic problems.


A simplified diagnostic work-up for the detection of gestational diabetes mellitus in low resources settings: achievements and challenges.
Modern strategies for the screening and diagnosis of Gestational Diabetes Mellitus (GDM) rely on universal Oral Glucose Tolerance Test (OGTT). However, they are unsustainable in low-income countries. In this study, we aimed at assessing the feasibility of a simplified diagnostic policy. The study took place in an urban referral hospital in Freetown, Sierra Leone. During an 11-month period, pregnant women were offered capillary blood test for glucose assessment. They could be screened at any time during pregnancy. GDM was diagnosed if fasting glucose was ≥ 92 mg/dl or if the OGTT was positive. The latter was prescribed only to women presenting after 24 weeks' gestation with at least one risk factor for GDM and fasting capillary glucose between 85 and 91 mg/dl. A definitive diagnosis required confirmation to this aim, women with values above the thresholds were invited to refer the next working day for repeating the test after fasting overnight. Overall, 7827 women were referred for screening, of whom 6872 (87%) underwent at least one capillary glucose assessment. However, 895 of those who had a positive test did not return for confirmation. Overall, a definite assessment could be done in 5799 subjects corresponding to 76% (95% CI 75-77%) of those eligible. GDM was diagnosed in 128 women (1.9%, 95% CI 1.6-2.2%). Based on an expected confirmation rate of 22% (calculated from those who referred for confirmation) in the 895 women who did not come back, one could infer that GDM would have been diagnosed in additional 197 women, raising the prevalence to 4.7% (95% CI 4.2-5.3%). Three quarters of subjects could be assessed with our approach. Data also suggest that GDM is not rare even if identification of affected cases remains challenging.


Circular RNA circLGMN facilitates glioblastoma progression by targeting miR-127-3p/LGMN axis.
Glioblastoma (GBM) is one of the most devastating cancers and is characterized by rapid cell proliferation and aggressive invasiveness. Legumain (LGMN), a substrate-specific protease, is associated with poor progression of GBM. Circular RNAs (circRNAs) are aberrantly expressed in various cancers and play crucial roles in tumor progression; however, the functional roles of circRNAs originating from LGMN remain largely unknown in GBM. Herein, we found that hsa_circ_0033009 (circLGMN) was the most abundantly expressed circRNA derived from LGMN. CircLGMN was upregulated in high-grade glioma (HGG), and high expression of circLGMN was associated with poor prognosis in patients with glioma. CircLGMN overexpression promoted GBM cell proliferation and enhanced cell invasion. Mechanistically, circLGMN acts as a sponge for miR-127-3p, and prevents miR-127-3p-mediated degradation of LGMN mRNA, ultimately leading to increased LGMN protein expression. Treatment with miR-127-3p mimic suppressed proliferation and reduced invasion of GBM cells overexpressing circLGMN. Moreover, circLGMN overexpression promoted GBM malignancy in vivo, while miR-127-3p overexpression alleviated this effect. Taken together, circLGMN is a novel tumor-promoting circRNA that acts by sponging miR-127-3p, which ultimately leads to LGMN upregulation. Thus, targeting the circLGMN/miR-127-3p/LGMN axis might be a promising strategy for GBM treatment. More importantly, the discovery of the self-regulatory mechanism of LGMN expression by circLGMN, will facilitate further research on LGMN.


Polymorphism of the major envelope glycoprotein (gp70) of murine C-type viruses: virion associated and differentiation antigens encoded by a multi-gene family.
Structural comparison of the major envelope glycoproteins (gp70) from 35 different murine type C viruses and free gp70 expressed at various anatomical sites in the mouse showed that the gp70s are polymorphic products of a large multi-gene family encoding viral and differentiation antigens. Different proviruses are expressed in cells following distinct pathways of differentiation. When the various gp70s are grouped according to primary structure they fall naturally into viral host range classes, confirming the suspicion that C-type viral tropism is largely determined by the nature of the gp70 product expressed.


[Central interdisciplinary emergency department. Organization of emergency medicine from the perspective of hospital management].
The treatment of emergencies in a hospital should be organized in a central interdisciplinary emergency department (ER). It is the main entrance for all patients with acute illness or injuries. There are multiple advantages of such a central unit. Quality of treatment and economic efficiency is improved. The interdisciplinary diagnostics and treatment at one place prevents time-consuming and unnecessary transport. The fact that more complex diseases and injuries need specialized doctors in specific disciplines should be considered in personnel planning of the ER. To reinsure that the entire medical staff of the hospital is familiar with the daily routine and clinical pathways of the ER, doctors from other departments of the hospital should always be part of the ER team.


Extraction of cage-like sporopollenin exine capsules from dandelion pollen grains.
Pollen-based microcapsules such as hollow sporopollenin exine capsules (SECs) have emerged as excellent drug delivery and microencapsulation vehicles. To date, SECs have been extracted primarily from a wide range of natural pollen species possessing largely spherical geometries and uniform surface features. Nonetheless, exploring pollen species with more diverse architectural features could lead to new application possibilities. One promising class of candidates is dandelion pollen grains, which possess architecturally intricate, cage-like microstructures composed of robust sporopollenin biopolymers. Here, we report the successful extraction and macromolecular loading of dandelion SECs. Preservation of SEC morphology and successful removal of proteinaceous materials was evaluated using scanning electron microscopy (SEM), matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry, elemental CHN analysis, dynamic image particle analysis (DIPA) and confocal laser scanning microscopy (CLSM). Among the tested processing schemes, acidolysis using 85% (v/v) phosphoric acid refluxed at 70 °C for 5 hours yielded an optimal balance of intact particle yield, protein removal, and preservation of cage-like microstructure. For proof-of-concept loading, bovine serum albumin (BSA) was encapsulated within the dandelion SECs with high efficiency (32.23 ± 0.33%). Overall, our findings highlight how hollow microcapsules with diverse architectural features can be readily prepared and utilized from plant-based materials.


Roflumilast--an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial.
Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation associated with chronic inflammation. There are few treatment options for the disease. This study assessed the efficacy and safety of roflumilast, a phosphodiesterase-4 inhibitor, in patients with moderate to severe COPD. This phase III, multicentre, double-blind, randomised, placebo-controlled study was undertaken in an outpatient setting. 1411 patients with COPD were randomly assigned roflumilast 250 microg (n=576), roflumilast 500 microg (n=555), or placebo (n=280) given orally once daily for 24 weeks. Primary outcomes were postbronchodilator FEV1 and health-related quality of life. Secondary outcomes included other lung function parameters and COPD exacerbations. Analyses were by intention to treat. 1157 (82%) patients completed the study; 32 (11%) withdrew from the placebo group, 100 (17%) from the roflumilast 250 microg group, and 124 (22%) from the roflumilast 500 microg group. Postbronchodilator FEV1 at the end of treatment significantly improved with roflumilast 250 microg (by 74 mL [SD 18]) and roflumilast 500 microg (by 97 mL [18]) compared with placebo (p<0.0001). Improvement in health-related quality of life was greater with roflumilast 250 microg (-3.4 units [0.6]) and roflumilast 500 microg (-3.5 units [0.6]) than with placebo (-1.8 units [0.8]), although the differences between treatment groups were not significant. The mean numbers of exacerbations per patient were 1.13 (2.37), 1.03 (2.33), and 0.75 (1.89) with placebo, roflumilast 250 microg, and roflumilast 500 microg, respectively. Most adverse events were mild to moderate in intensity and resolved during the study. Roflumilast is a promising candidate for anti-inflammatory COPD treatment because it improved lung function and reduced exacerbations compared with placebo. Long-term studies are needed to fully assess the effect on health-related quality of life.


Trifluoperazine antagonizes inhibition of renin release by angiotensin II.
The influence of trifluoperazine (TFP) treatment on angiotensin II-induced inhibition of renin release from the rat isolated perfused kidney was examined. Angiotensin II, 1 mumol/l, in the presence of 1 mmol/l calcium, reduced basal renin secretion by 70%. When calcium was omitted from the perfusion medium, inhibition of renin release no longer occurred. Pretreatment of the rat isolated perfused kidney with the calmodulin inhibitor trifluoperazine (TFP), 10 mumol/l for 6 min, interfered with the inhibitory action of angiotensin II on renin release as well as angiotensin II-induced renal vasoconstriction. Our data suggest a role for calmodulin in mediating the effects of angiotensin II on both renin release and renal vascular resistance.


Investigations on the primary structure of human plasminogen. Further evidence for sequence homology.
NH2-Terminal sequences were determined by the automated Edman method in four fragments which were isolated from a mixture of fragments obtained by CNBr cleavage of human plasminogen. One of the fragments whose sequence was determined over the first 31 residues shows sequence homologies with the fragment that forms the linkage between the plasmin chains and also with the non-thrombin part of prothrombin.


Fecal but not serum calprotectin is a potential marker of GVHD after stem cell transplantation.
Gastrointestinal graft-versus-host disease (GvHD) represents a life-threatening complication after stem cell transplantation. Differential diagnosis between gut GvHD and other causes of diarrhea after HSCT is still subjected to endoscopy and histological findings. The research for a reliable biomarker for gut GvHD might allow an early diagnosis of this condition and a consequent prompt treatment that could reduce unfavorable outcomes. Recently, fecal calprotectin was reported as reliable marker of gut involvement. We would evaluate if serum instead of fecal calprotectin could be considered a possible biomarker of gut GvHD. Serum calprotectin was measured in a cohort of 54 patients submitted to allogeneic stem cell transplantation using ELISA assay. For a subset of 21 patients, calprotectin serum levels were compared with fecal calprotectin detection. Contrary to fecal calprotectin, we found only a trend to high level of serum calprotectin for GvHD development and gut involvement, but statistical difference was not reached. Fecal but not serum calprotectin could be considered as possible biomarker for gut GvHD.


Xanthoma disseminatum. Report of a case, with histological and ultrastructural studies of skin lesions.
A patient with xanthoma disseminatum with typical xanthomatous lesions on the flexural surfaces and diabetes insipidus controllable by 1.5 gm daily administration of clofibrate was examined. Acid orcein and Giemsa stain of biopsy material revealed dark brown masses within the cytoplasm of histiocytes or giant cells, which were demonstrated to be elastic fibers engulfed by the tissue macrophages on electron microscopy. Numerous phagosomes, vacuoles, and concentric lamellar structures were present in the cytoplasm of the tissue macrophages. Collagen fibers were also altered in the lesion. Occasional crystals suggesting cholesterol were also found. However, no Langerhans' cell granules were found within any dermal macrophages; this indicated that these histiocytes or macrophages were different from those in histiocytosis X. It was suggested that autophagocytosis of tissue components is one of the pathologic features in the cutaneous lesion of xanthoma disseminatum.


Vibrotactile and temperature sensory interaction in the human tongue.
Lingual vibrotactile thresholds were used to demonstrate an interaction between the lingual senses of vibrotaction and temperture. Thresholds were obtained on 10 Ss from the anterior midline of the lingual dorsum at a frequency of 250 Hz. Five temperature conditions were tested ranging in 10 degrees C steps from 17 degrees C to 57 degrees C. Thresholds were obtained before and after the introduction of the temperature stimuli. Comparison of mean pre- and post-experimental thresholds demonstrated that temperature is a determining factor in lingual vibrotactile threshold values. The data indicated that systematic variation from normal body temperature resulted in corresponding decreases in lingual vibrotactile sensitivity. Diagnostic and clinical implications of this interaction were discussed.


Similarities in food preferences between children and their siblings and parents.
Fifty-five Canadian women completed questionnaires about the food likes and dislikes of members of their families. Each family consisted of a mother, a father, a "target" child (24-83 months old) and the child's nearest-age sibling. The likes and dislikes of the target children were cross-tabulated with those of their mothers, fathers, and siblings, and phi-statistics were computed for the child-mother, child-father and child-sibling pairs as measures of similarity in food preferences. The results revealed that the target children resembled all three members of their families in their food preferences and that this resemblance was especially pronounced in the case of siblings.


Isolation of the outer membrane of Branhamella catarrhalis.
The emergence of Branhamella catarrhalis as an important human pathogen has stimulated interest in investigations of the outer membrane (OM) of the bacterium. In this study, the OM of B. catarrhalis was isolated and partially characterized. Radiolabelled cells were lysed and fractionated by isopycnic centrifugation in a continuous sucrose gradient. Five fractions were identified. Fraction A consisted of OM fragments of varying density. Fractions B and C were OM of a discrete density containing some cytoplasmic membrane. Fraction D was cytoplasmic membrane and Fraction E contained smaller less dense fragments of cytoplasmic membrane. The protein composition of the Branhamella OM is typical for that of Gram-negative bacteria in that approximately 10 to 20 proteins were present with six to eight of these proteins predominating. Having isolated and partially characterized the OM by sucrose density centrifugation, five simpler techniques for isolating OM were employed and the preparations compared to OM isolated on the gradient. Techniques that are based on differential detergent solubility of OM and cytoplasmic membrane were ineffective in isolating OM of B. catarrhalis. By contrast, techniques that involved collection of OM vesicles were successful in isolating OM of B. catarrhalis. Collection of vesicles from broth culture supernatants and EDTA-heat-induced vesicles were identified as convenient and reliable methods for isolating OM. Isolating and partially characterizing the OM of B. catarrhalis represents an initial step in a systematic study of outer membrane antigens of the bacterium.


[Study of the influence of culture duration on the development of implanted male genital disks in larvae ofEphestia kuehniella Z.]
Complete and bisected male genital disks (HO) from full-grown (T9) larvae were transplanted either into larvae and pharate pupae of different age (T4, T7, T9 larvae, A1-A5 pharate pupae) or repeatedly transferred into full-grown larvae before being implanted into a final larval host. After metamorphosis of the hosts, most of the complete transplants and regenerated HO halves showed normal morphological features, but the implanted genitals from old pharate pupae (A4 and A5) were abnormally differentiated. Frequency of Regeneration. After transplanting both halves of the bisected HO into T9 hosts, three groups of results were observed: (1) each of the two halves regenerated into a complete genital organ; (2) only one half regenerated; (3) neither of the two halves regenerated. In the pharate pupae no regeneration of the implanted halves took place. If the lapse of time between the transplantation and, the onset of metamorphosis (=onset of pharate pupae phase) was long enough by transplanting into young larvae (T4) or by repeatedly transferring into old larvae and subsequent transplantation into a final larval host, all the implanted halves were able to regenerate. Size of the Implanted Genital Organs After prolonging the in vivo culture in larval hosts by implanting into young larvae or repeatedly transferring into old larvae, it was found that the regenerated genitalia grew to the same size as the complete transplants, but the size of the complete transplants increased, if at all, only insignificantly. Duration of Development of the Hosts. Regeneration of one HO half implanted into a full-grown larva caused an average delay of further development of about 2 days. An additional delay was recorded when both halves had regenerated. However, no delay was observed when HO halves implanted into young (T4) larvae regenerated, and no delay occurred in the final hosts when the repeatedly transferred halves had reached a certain stage of regeneration.The developmental capacities of the tranplanted disks and the control of metamorphosis by regenerating disks are discussed.


Skin diseases of children in Mali: a public health problem.
In order to estimate the importance as a public health problem of skin diseases, we investigated the prevalence and severity of skin diseases in a representative sample of children in Mali. 1817 children were randomly selected in 30 clusters by probability-proportional-to-size sampling in Koulikoro region. The mean prevalence (+/- 2 SD) of skin diseases was 34 +/- 4%. The most frequent dermatoses were pyoderma (12.3 +/- 1.6%), tinea capitis (9.5 +/- 2.5%), pediculosis capitis (4.7 +/- 1.4%), scabies (4.3 +/- 1.5%), and molluscum contagiosum (3.6 +/- 1%). The most troublesome dermatoses were scabies and severe pyoderma. Pyoderma was the only dermatosis associated with poor individual or household hygiene. Public health services were little used by the population for skin diseases, probably because of the lack of an adequate response by the services and the high cost of treatment. The high prevalence and the severity of many of the lesions, and the discomfort caused, make pyoderma and scabies a significant public health problem in Mali.


Gross bilateral reflux in infants: gradual decrease of initial detrusor hypercontractility.
We performed followup investigations of the urodynamic patterns of 11 boys with gross bilateral reflux, which are sometimes characterized by low bladder capacity and hypercontractility of the detrusor. Urodynamic evaluations were done a mean of 2 years after the initial assessment during infancy. Initial hypercontractility resolved and bladder capacity increased from below normal to high in the majority of cases. The number of children with instability did not change significantly. The urodynamic pattern at followup was similar to that previously reported as the most common dysfunction in older children with reflux.


The impact of obstructive sleep apnea on bronchiolitis severity in children with Down syndrome.
Acute bronchiolitis commonly causes respiratory failure in children ≤2 years, and is particularly severe in those with Down syndrome (DS). Obstructive sleep apnea (OSA), common in DS, is also associated with respiratory complications. However, it is unknown whether OSA is associated with worse outcomes in children with and without DS, hospitalized with bronchiolitis. We hypothesized that in children with bronchiolitis, OSA is associated with worse outcomes in those with DS, independent of DS-related comorbidities. Hospital discharge records of children with bronchiolitis aged ≤2 years were obtained for 1997-2012 from the Kid's Inpatient Database. The primary outcome was invasive mechanical ventilation (IMV), and secondary outcomes were non-invasive mechanical ventilation (NIMV), length of hospital stay, and inflation-adjusted cost of hospitalization (IACH). Multivariable regression was conducted to ascertain the associations between OSA and primary and secondary outcomes accounting for DS-associated comorbidities. There were 928,961 hospitalizations for bronchiolitis. The DS group with bronchiolitis (n = 8697) was more likely to have OSA [241 (2.77%) vs 1293 (0.14%), p < 0.001] compared to the non-DS group (n = 920,264). Multivariable logistic regression showed that OSA was associated with IMV (adjusted odds ratio [OR], 3.32 [95% CI 2.54-4.35], p < 0.0001) in all children with bronchiolitis; and in those with DS, it was associated with IMV (adjusted OR, 2.34 [95% CI 1.38-3.97], p = 0.002), NIMV (adjusted OR, 8.21 [95% CI 4.48-15.04], p < 0.0001) and IACH (adjusted β, 0.18 [95% CI 0.02-0.34], p = 0.031). OSA is independently associated with assisted ventilation in all children hospitalized with bronchiolitis, regardless of DS-associated comorbidities in those with DS. The severity of bronchiolitis in children with DS may be driven by the high prevalence of OSA.


Evolutionary origins of chemical synapses.
Synaptic transmission is a fundamental neurobiological process by which neurons interact with each other and non-neuronal cells. It involves release of active substances from the presynaptic neuron onto receptive elements of postsynaptic cells, inducing waves of spreading electrochemical response. While much has been learned about the cellular and molecular mechanisms driving and governing transmitter release and sensing, the evolutionary origin of synaptic connections remains obscure. Herein, we review emerging evidence and concepts suggesting that key components of chemical synapse arose independently from neurons, in different functional and biological contexts, before the rise of multicellular living forms. We argue that throughout evolution, distinct synaptic constituents have been co-opted from ancestral forms for a new role in early metazoan, leading to the rise of chemical synapses and neurotransmission. Such a mosaic model of the origin of chemical synapses agrees with and supports the pluralistic hypothesis of evolutionary change.


Corrections for Rabi oscillations in cardiac chemical exchange saturation transfer MRI under the influence of very short preparation pulses.
Very short chemical exchange saturation transfer (CEST) pulses are beneficial in cardiac continuous wave (cw) CEST MRI, especially in small animals because of their rapid heartbeat; however, they result in signal modulations caused by Rabi oscillations. Therefore, we implemented two different filter techniques, DOwnsampling by SEparation of CEST spectrum into two parts (DOSE) and time domain (TD)-based filtering, to correct for these signal corruptions, allowing a reliable quantification of glucose-weighted CEST (glucoCEST) MRI contrast. In our study, cw CEST measurements were performed on a 9.4-T small animal BioSpec system using CEST pulses in the range of 10 to 200 ms. Experimental dependencies of Rabi oscillations on key MRI parameters were validated by Bloch-McConnell (BM) simulations. Filter efficiency was explored in a glucose concentration series as well as in the myocardium of healthy mice (n = 8), and glucoCEST contrast was subsequently quantified. The experimental results showed that the impact of Rabi oscillations on CEST spectra increased with decreasing CEST pulse length, optimized B0 homogeneity, and shorter T2 relaxation time, in accordance with results from BM simulations. Both investigated filter techniques reduced these signal modulations significantly, with DOSE filtering preserving the amplitude and TD filtering the spectral information of CEST data more accurately. Upon filter application, a significant decrease in glucoCEST contrast in the myocardium of healthy mice was observed after glucose infusion (pTD = 0.0079, pDOSE = 0.0044). To conclude, this study offers comprehensive experimental insights into Rabi oscillations within CEST MRI data along with methodological considerations that could be further advanced into a robust and precise cardiac cw CEST protocol by integrating DOSE and TD filtering into the standard CEST analysis pipeline.


Mean magnetic susceptibility regularized susceptibility tensor imaging (MMSR-STI) for estimating orientations of white matter fibers in human brain.
An increasing number of studies show that magnetic susceptibility in white matter fibers is anisotropic and may be described by a tensor. However, the limited head rotation possible for in vivo human studies leads to an ill-conditioned inverse problem in susceptibility tensor imaging (STI). Here we suggest the combined use of limiting the susceptibility anisotropy to white matter and imposing morphology constraints on the mean magnetic susceptibility (MMS) for regularizing the STI inverse problem. The proposed MMS regularized STI (MMSR-STI) method was tested using computer simulations and in vivo human data collected at 3T. The fiber orientation estimated from both the STI and MMSR-STI methods was compared to that from diffusion tensor imaging (DTI). Computer simulations show that the MMSR-STI method provides a more accurate estimation of the susceptibility tensor than the conventional STI approach. Similarly, in vivo data show that use of the MMSR-STI method leads to a smaller difference between the fiber orientation estimated from STI and DTI for most selected white matter fibers. The proposed regularization strategy for STI can improve estimation of the susceptibility tensor in white matter.


Cool enough? Lessons learned from cryoballoon-guided catheter ablation for atrial fibrillation in young adults.
Cryoballoon (CB)-guided ablation of atrial fibrillation (AF) is established in symptomatic AF patients. This study sought to determine the safety and efficacy of CB pulmonary vein isolation (PVI) in young adults. A total of 93 consecutive patients aged <45 years referred to our center for AF ablation were included in this observational study. All patients received CB-guided PVI according to a standardized institutional protocol. Follow-up was performed in our outpatient clinic using 72-h Holter monitoring and periodic telephone interview. Recurrence was defined as any AF/atrial tachycardia (AT) episode >30 s following a 3-month blanking period. A propensity matched control group consisting of patients older than 45 years were used for further evaluation. Mean age was 35 ± 7 years, 22% suffered from persistent AF, 85% were male. Mean follow-up was 2.6 ± 2 years. At the end of the observational period, 83% of patients were free of any AF/AT episodes. There was an excellent overall 12-month success rate of 92%. In comparison to a matched group the overall recurrence rate was noticeably lower in the young group (15% vs. 27%). Increasing age was associated with a hazard ratio of 1.16 for recurrence. In a multivariate analysis model, left atrial diameter remained as significant predictor of AF/AT recurrence. The complication rate was low, no permanent phrenic nerve palsy was observed. CB-guided PVI in young adults is safe and effective with favorable long-term results. It may be considered as first-line therapy in this relatively healthy population.


[Clinical pathology of chronic hyperplastic laryngitis. 2. Clinical, morphological and statistical studies with special reference to precancerous changes].
Data on 13 different clinical, histological and environmental factors were obtained from 54 patients with hyperplastic laryngitis (HL). They were evaluated by multiple linear factor analysis. HL can be considered to be a complex clinico-morphological entity. Precancerous changes in the larynx were closely correlated with the grade of HL. Etiologically only a weak association with tobacco and alcohol use could be found. The development of the disease was independent of age, sex, nasal function and of other chemical, physical or mechanical factors.


[Clinical picture of prenatal virus infections].
Review about virus infections in pregnancy. The kind of damage, the incidence, the diagnostic possibilities and the management are discussed.


Bacterial heavy metal resistance related to environmental conditions.
Contaminated water bodies such as rivers provide reservoirs for bacterial resistance. This field study tested the water quality and the bacterial resistance to heavy metals of Qishan River water pollution. Wastewater discharged to environmental surface waters is a major pathway of heavy metals and heavy metal-resistant bacteria. Contaminated water bodies such as rivers provide reservoirs for bacterial resistance. This field study tested the water quality and bacterial resistance to heavy metals of Qishan River water pollution. Guided by our research hypothesis that an overall increase in downstream heavy metal resistance levels was following an increase in human settlements were eight sites sampled along the Qishan River. These were situated upstream and downstream to the confluence of the Qishan River with the Kaoping River. In the laboratory bacterial heavy metal resistance was bio-assayed by disk diffusion and micro-dilution with six widely used heavy metals. The comparison of bacterial resistance was among Qishan River upstream sites (sites 1-6) and downstream sites (sites 7-9). Multi-drug-resistant bacteria and co-resistance against heavy metals and antibacterials appeared at site 8. This research discusses the correlation between environmental factors, and antibacterial and heavy metal resistance. The results provide stakeholders and authorities responsible for environmental pollution with a reference for risk assessment and management of bacterial resistance.


Detection of single nucleotide polymorphism in the para-sodium channel gene of Rhipicephalus annulatus populations from Egypt resistant to deltamethrin.
Rhipicephalus annulatus field populations collected from small cattle farms in Beni-Suef province in Egypt were evaluated for deltamethrin resistance by toxicological in vitro bioassays (adult immersion test-AIT and larval packet test-LPT). Moreover, a quantitative PCR high resolution melting (PCR-HRM) technique was used to detect nucleotide substitutions in the voltage-gated sodium channel (Na-channel) gene. By the in vitro bioassays, the examined ticks were phenotypically categorized as deltamethrin susceptible (populations El-Wasta - A, and El-Hakamna - C) or resistant (populations El-Wasta - B, El-Hakamna - D, EL-Halabia - E, and Kom-abokhalad - F). Based on LPT findings, the phenotypic resistant populations were found to have a resistance ratio between 6.5 - 10.8. The PCR-HRM genotyping of the ticks showed variable melting curves among the populations in domain II of the Na-channel gene. Analysis of the curves showed the presence of wild type, mutant homozygous, and mutant heterozygous tick individuals. By sequencing the PCR amplified fragments, the C190A mutation was the only detected nucleotide polymorphism of domain II among the phenotypically resistant populations, which was present in 39.5 % (34/86) of the ticks tested. On the other hand, the phenotypically susceptible populations A and C did not show C190A mutant homozygous (RR) individuals. Meanwhile, in domain III all of the examined populations revealed melting curves like the wild type. Furthermore, the sequence analysis of these populations confirmed the absence of SNPs in domain III. The C190A single point mutation was detected for the first time in domain II of the Na-channel gene of deltamethrin-resistant R. annulatus in Egypt using PCR-HRM. Screening for efficacy of chemical compounds used by farmers to control ticks on cattle should be considered as part of animal health programs to manage the emerging resistance to acaricides in R. annulatus populations.


Natural linewidth chemical shift imaging (NL-CSI).
The discrete Fourier transform (FT) is a conventional method for spatial reconstruction of chemical shifting imaging (CSI) data. Due to point spread function (PSF) effects, FT reconstruction leads to intervoxel signal leakage (Gibbs ringing). Spectral localization by imaging (SLIM) reconstruction was previously proposed to overcome this intervoxel signal contamination. However, the existence of magnetic field inhomogeneities creates an additional source of intervoxel signal leakage. It is demonstrated herein that even small field inhomogeneities substantially amplify intervoxel signal leakage in both FT and SLIM reconstruction approaches. A new CSI data acquisition strategy and reconstruction algorithm (natural linewidth (NL) CSI) is presented that eliminates effects of magnetic field inhomogeneity-induced intervoxel signal leakage and intravoxel phase dispersion on acquired data. The approach is based on acquired CSI data, high-resolution images, and magnetic field maps. The data are reconstructed based on the imaged object structure (as in the SLIM approach) and a reconstruction matrix that takes into account the inhomogeneous field distribution inside anatomically homogeneous compartments. Phantom and in vivo results show that the new method allows field inhomogeneity effects from the acquired MR signal to be removed so that the signal decay is determined only by the "natural" R2 relaxation rate constant (hence the term "natural linewidth" CSI).


Absence of myoepithelial cells correlates with invasion and metastasis of Carcinoma ex pleomorphic adenoma.
Myoepithelial cells (MECs) are implicated in the development and progression of human salivary gland tumours. Here, we investigate the potential role for MECs in invasion and metastasis of carcinoma ex pleomorphic adenoma (CXPA). Tumour tissues from 40 CXPA patients diagnosed between 1960 and 2014 were obtained. Patient samples were divided into two groups (non-invasive tumours, n=10; and frankly invasive tumours, n=30). Each group was further divided into two subgroups (metastatic tumours and non-metastatic tumours). Immunohistochemistry for MEC markers (α-SMA, CALPONIN, and p63) was performed, and the number and distribution of MECs was quantified. For non-invasive CXPAs, non-metastatic cases (n=8) displayed a significant enrichment in CALPONIN(+) and α-SMA(+) MECs, but not p63(+) MECs, compared with metastatic cases (n=2). Likewise, for frankly invasive CXPAs (n=30), non-metastatic cases showed a significant enrichment for α-SMA(+), CALPONIN(+), and p63(+) MECs compared with metastatic cases (n=15). We demonstrate that non-invasive CXPAs have the potential for metastasis. Furthermore, the tumour capsule may not be the only barrier preventing invasion and metastasis, as a significant reduction in numbers of myoepithelial cells correlates with invasion and metastasis in CXPA patients.


Dynamical Simulations of Carotenoid Photoexcited States Using Density Matrix Renormalization Group Techniques.
We present a dynamical simulation scheme to model the highly correlated excited state dynamics of linear polyenes. We apply it to investigate the internal conversion processes of carotenoids following their photoexcitation. We use the extended Hubbard-Peierls model, H^UVP, to describe the π-electronic system coupled to nuclear degrees of freedom. This is supplemented by a Hamiltonian, H^ϵ, that explicitly breaks both the particle-hole and two-fold rotation symmetries of idealized carotenoid structures. The electronic degrees of freedom are treated quantum mechanically by solving the time-dependent Schrödinger equation using the adaptive time-dependent DMRG (tDMRG) method, while nuclear dynamics are treated via the Ehrenfest equations of motion. By defining adiabatic excited states as the eigenstates of the full Hamiltonian, H^=H^UVP+H^ϵ, and diabatic excited states as eigenstates of H^UVP, we present a computational framework to monitor the internal conversion process from the initial photoexcited 11Bu+ state to the singlet triplet-pair states of carotenoids. We further incorporate Lanczos-DMRG to the tDMRG-Ehrenfest method to calculate transient absorption spectra from the evolving photoexcited state. We describe in detail the accuracy and convergence criteria for DMRG, and show that this method accurately describes the dynamical processes of carotenoid excited states. We also discuss the effect of the symmetry-breaking term, H^ϵ, on the internal conversion process, and show that its effect on the extent of internal conversion can be described by a Landau-Zener-type transition. This methodological paper is a companion to our more explanatory discussion of carotenoid excited state dynamics in Manawadu, D.; Georges, T. N.; Barford, W. Photoexcited State Dynamics and Singlet Fission in Carotenoids. J. Phys. Chem. A 2023, 127, 1342.


What clinical practice strategies have been shown to decrease incidence rates of intraventricular haemorrhage in preterm infants?
To answer the clinical question 'In infants about to be delivered and admitted to neonatal units, what clinical practice strategies, compared to standard care, have been shown to decrease incidence rates of intraventricular haemorrhage (IVH)?' MEDLINE via Ovid (1943 to 5 January 2018), Embase via Ovid (1974 to 5 January 2018) and the Cochrane Library (5 January 2018) were searched for relevant articles. A total of 478 articles, after the removal of duplicates, were found and screened by title and abstract. Forty full-text articles were subsequently reviewed, and 19 were included as relevant to the structured clinical question. An additional article was included based on expert advice. There are various levels of research evidence for clinical practice strategies to decrease the incidence rates of IVH. Higher-quality evidence suggests that antenatal corticosteroids decrease the rates of IVH, and multiple evidence-based intervention bundles implemented in the neonatal unit are associated with decreased rates of IVH.


Clinical Utility of Rapid On-Site Evaluation of Touch Imprint Cytology during Cryobiopsy for Peripheral Pulmonary Lesions.
Cryobiopsy enables us to obtain larger specimens than conventional forceps biopsy despite the caution regarding complications. This study aimed to evaluate the clinical utility of rapid on-site evaluation of touch imprint cytology (ROSE-TIC) during cryobiopsy of peripheral pulmonary lesions (PPLs). We retrospectively reviewed the data of consecutive patients who underwent cryobiopsy for solid PPLs between June 2020 and December 2021. ROSE-TIC was performed on the first specimen obtained via cryobiopsy and assessed using Diff-Quik staining. The results of ROSE-TIC for each patient were compared with the histological findings of the first cryobiopsy specimen. Sixty-three patients were enrolled in this study. Overall, 57 (90.5%) lesions were ≤30 mm in size and 37 (58.7%) had positive bronchus signs. The radial endobronchial ultrasound findings were located within and adjacent to the lesion in 46.0% and 54.0% of the cases, respectively. The sensitivity, specificity, and positive and negative predictive values of the ROSE results for histological findings of the corresponding specimens were 69.8%, 90.0%, 93.8%, and 58.1%, respectively. The concordance rate was 76.2%. In conclusion, ROSE-TIC, due to its high specificity and positive predictive value, may be a potential tool in deciding whether cryobiopsy sampling could be finished during bronchoscopy.


Chlamydia pneumoniae (C. pneumoniae) infection upregulates atherosclerosis-related gene expression in human umbilical vein endothelial cells (HUVECs).
There is accumulating evidence that supports a role of infection in atherosclerosis, with possible mechanism by injuring to the endothelium and inducing an autoimmune response to heat shock proteins (HSPs). In this study, a cDNA array, containing 588 human cardiovascular genes, was utilized to analyze the gene expression profile of Chlamydia pneumoniae (C. pneumoniae) infected human umbilical vein endothelial cells (HUVECs). After 48h of C. pneumoniae infection, the HUVECs were harvested and subjected to immunofluorescent staining, electron microscopy, cDNA array hybridization, RT-PCR, and immunoblotting. This study found a panel of human host genes that were upregulated by C. pneumoniae. The majority of these genes were related to complex lipid metabolism, adhesion receptors, hormones, hormone receptors, and a metalloproteinase that may contribute to atherosclerosis in vivo. Representatives of upregulated gene products, i.e., heat shock protein 60 (HSP60), macrophage scavenger receptor, cytochrome P450, and VEGF165R were immunofluorescently detected in HUVECs, with their greater expression induced by C. pneumoniae infection. These findings supported the opinion that C. pneumoniae might contribute to atherosclerotic development in vivo.


Diaryl-substituted thiosemicarbazone: A potent scaffold for the development of New Delhi metallo-β-lactamase-1 inhibitors.
The superbug infection caused by New Delhi metallo-β-lactamase (NDM-1) has become an emerging public health threat. Inhibition of NDM-1 has proven challenging due to its shuttling between pathogenic bacteria. A potent scaffold, diaryl-substituted thiosemicarbazone, was constructed and assayed with metallo-β-lactamases (MβLs). The obtained twenty-six molecules specifically inhibited NDM-1 with IC50 0.038-34.7 µM range (except 1e, 2e, and 3d), and 1c is the most potent inhibitor (IC50 = 0.038 µM). The structure-activity relationship of synthetic thiosemicarbazones revealed that the diaryl-substitutes, specifically 2-pyridine and 2-hydroxylbenzene improved inhibitory activities of the inhibitors. The thiosemicarbazones exhibited synergistic antimycobacterial actions against E. coli-NDM-1, resulted a 2-512-fold reduction in MIC of meropenem, while 1c restored 16-256-, 16-, and 2-fold activity of the antibiotic on clinical isolates ECs, K. pneumonia and P. aeruginosa harboring NDM-1, respectively. Also, mice experiments showed that 1c had a synergistic antibacterial ability with meropenem, reduced the bacterial load clinical isolate EC08 in the spleen and liver. This work provided a highly promising scaffold for the development of NDM-1 inhibitors.


Whole-brain studies of spontaneous behavior in head-fixed rats enabled by zero echo time MB-SWIFT fMRI.
Understanding the link between the brain activity and behavior is a key challenge in modern neuroscience. Behavioral neuroscience, however, lacks tools to record whole-brain activity in complex behavioral settings. Here we demonstrate that a novel Multi-Band SWeep Imaging with Fourier Transformation (MB-SWIFT) functional magnetic resonance imaging (fMRI) approach enables whole-brain studies in spontaneously behaving head-fixed rats. First, we show anatomically relevant functional parcellation. Second, we show sensory, motor, exploration, and stress-related brain activity in relevant networks during corresponding spontaneous behavior. Third, we show odor-induced activation of olfactory system with high correlation between the fMRI and behavioral responses. We conclude that the applied methodology enables novel behavioral study designs in rodents focusing on tasks, cognition, emotions, physical exercise, and social interaction. Importantly, novel zero echo time and large bandwidth approaches, such as MB-SWIFT, can be applied for human behavioral studies, allowing more freedom as body movement is dramatically less restricting factor.


Oxidation of 2,4-dichlorophenol in saline water by unactivated peroxymonosulfate: Mechanism, kinetics and implication for in situ chemical oxidation.
Inorganic and organic pollutants present a hazard to surface and groundwater resources. Peroxymonosulfate (PMS, HSO5-) has received increasing attention for in situ chemical oxidation (ISCO) capable of remediating contaminated sites. Considering that saline waters occur widely in natural environments, it is desirable to evaluate the effect of Cl- on the PMS oxidation of organic compounds. In this study, 2,4-dichlorophenol (2,4-DCP) was used as a model pollutant. At a PMS concentration of 2.0 mM, Cl- concentration of 50 mM, and solution pH of 7.0, 2,4-DCP was completely degraded by PMS in the presence of Cl- (PMS/Cl- system), while PMS alone exhibited almost no reactivity with 2,4-DCP. The degradation of 2,4-DCP was optimized at a solution pH of 8.4 and high concentrations of PMS and Cl-. Quenching experiments and degradation pathway analyses indicated that HClO was responsible for 2,4-DCP oxidation, and HClO was mainly generated by the interaction of Cl- with HSO5-, rather than SO52-. Consequently, the transformation from HSO5- to HClO appeared under a solution pH of 10.0 and was favored in an acidic solution. Given the ambient pH and Cl- concentrations of saline waters, a considerable amount of HClO may be produced by the interaction of PMS with Cl- in the oxidant delivery stage of ISCO processes. Interestingly, H2O2 and peroxydisulfate did not exhibit reactions similar to those of PMS. This research indicated that caution must be exercised when choosing an oxidant for ISCO processes in saline waters.


A field survey on elution of lead and nickel from taps used in homes and analysis of product test results.
The elution of lead, and nickel from water supply devices into water is a potential health concern. This study was performed to examine the actual concentrations of nickel and lead in the water from taps in homes and offices, focusing on the differences between first flush and fully flushed water. The water quality management target value and water quality standard in Japan specify nickel and lead concentrations in drinking water <20 and <10 μg/L, respectively. Nickel concentration in the first flush water (100 mL) from 110 household taps revealed 22 cases (20%) > 20 μg/L, while the fully flushed water satisfied the standard after running 5000 mL of water. The nickel concentration decreased gradually in sequential sampling of each 100 mL from the taps. Lead concentration in the first flush water exceeded the standard in 32 cases (29%), while the fully flushed water was below the target value. The concentration in the first flush water tended to decrease with time since the tap installation, and this was significant after 10 years for nickel but not significant for lead. It is important to flush retained water out of the tap after several hours without use. No significant correlation was found with the volume of the test faucet in the market, but bronze-based products showed higher nickel concentrations than brass and plastic products.


Species dispersal along rivers and streams may have variable importance to metapopulation structure.
The ability to prioritize habitats that have spatially varied contributions to species persistence can produce synergistic benefits for regional conservation efforts. However, conservation in spatially diverse landscape-networks requires considering dispersal asymmetry in the context of ecological connectivity and metapopulation persistence. By developing an approach based on metapopulation theory, this study prioritized the importance of habitat (as determined by the habitat quality and spatial position in networks) on metapopulation structure in mountainous streams. As a case study, we examined dispersal via overland and instream networks in a riverine mayfly Rhithrogena sp. cf. japonica in a mountain range of Southwest China. Compared to flow velocity, water depth, and instream nutrient-levels, water temperature was a key factor in determining local habitat suitability for R. sp. cf. japonica. Higher water temperature was linked to poor habitat suitability. Instream pathways were the main dispersal corridors compared with overland movement between tributaries for this mayfly. In basins on the east aspect of this mountain range, either monotonically increasing (i.e., never decreasing) or unimodal (i.e., with a single peak) patterns demonstrated the importance of riverine habitats that occur along elevational gradients. However, the importance of habitat appeared to show no definite patterns with elevation on the west aspect. In terms of metapopulation structure, local quality of habitat contributed more to the regional importance of habitat than its spatial position in the networks. The framework presented highlights that the importance of riverine habitats may be quite variable in species having directional dispersal networks across the fluvial landscape in mountainous areas. Results from this framework can serve as the basis to apply a mechanistic understanding to managing and protecting native populations through regional restoration actions.


Correlation of open cell-attached and excised patch clamp techniques.
The excised patch clamp configuration provides a unique technique for some types of single channel analyses, but maintenance of stable, long-lasting preparations may be confounded by rundown and/or rapid loss of seal. Studies were performed on the amiloride-sensitive Na+ channel, located on the apical surface of A6 cells, to determine whether the nystatin-induced open cell-attached patch could serve as an alternative configuration. Compared to excised inside-out patches, stable preparations were achieved more readily with the open cell-attached patch (9% vs. 56% of attempts). In both preparations, the current voltage (I-V) relation was linear, current amplitudes were equal at opposite equivalent clamped voltages, and Erev was zero in symmetrical Na+ solutions, indicating similar Na+ activities on the cytosolic and external surfaces of the patch. Moreover, there was no evidence that nystatin altered channel activity in the patch because slope conductance (3-4pS) and Erev (75 mV), when the bath was perfused with a high K:low Na solution (ENa = 80 mV), were nearly equal in both patch configurations. Our results therefore indicate that the nystatin-induced open cell-attached patch can serve as an alternative approach to the excised inside-out patch when experiments require modulation of univalent ions in the cytosol.


MULTI: a shared memory approach to cooperative molecular modeling.
A general purpose molecular modeling system, MULTI, based on the UNIX shared memory and semaphore facilities for interprocess communication is described. In addition to the normal querying or monitoring of geometric data, MULTI also provides processes for manipulating conformations, and for displaying peptide or nucleic acid ribbons, Connolly surfaces, close nonbonded contacts, crystal-symmetry related images, least-squares superpositions, and so forth. This paper outlines the basic techniques used in MULTI to ensure cooperation among these specialized processes, and then describes how they can work together to provide a flexible modeling environment.


Effects of Extra-Long-Acting Recombinant Bovine FSH (bscrFSH) on Cattle Superovulation.
Over the last few years, several commercial FSH products have been developed for cattle superovulation (SOV) purposes in Multiple Ovulation and Embryo Transfer (MOET) programs. The SOV response is highly variable among individuals and remains one of the main limiting factors in obtaining a profitable number of transferable embryos. In this study, follicle stimulating hormone (FSH) from different origins was included in two SOV protocols, (a) FSH from purified pig pituitary extract (NIH-FSH-p; two doses/day, 12 h apart, four consecutive days); and (b) extra-long-acting bovine recombinant FSH (bscrFSH; a single dose/day, four consecutive days), to test the effects of bscrFSH on the ovarian response, hormone profile levels, in vivo embryo production and the pluripotency gene expression of the obtained embryos. A total of 68 healthy primiparous red Angus cows (Bos taurus) were randomly distributed into two experimental groups (n = 34 each). Blood sample collection for progesterone (P4) and cortisol (C) level determination was performed together with ultrasonographic assessment for ovarian size, follicles (FL) and corpora lutea (CL) quantification in each SOV protocol (Day 0, 4, 8, and 15). Moreover, FSH profiles were monitorised throughout both protocols (Day 0, 4, 5, 6, 7, 8, 9, 10, and 15). In vivo embryo quantity and quality (total structures, morulae, blastocysts, viable, degenerated and blocked embryos) were recorded in each SOV protocol. Finally, embryo quality in both protocols was assessed by the analysis of the expression level of crucial genes for early embryo development (OCT4, IFNt, CDX2, BCL2, and BAX). P4 and cortisol concentration peaks in both SOV protocols were obtained on Day 15 and Day 8, respectively, which were statistically different compared to the other time-points (p < 0.05). Ovarian dimensions increased from Day 0 to Day 15 irrespective of the SOV protocol considered (p < 0.05). Significant changes in CL number were observed over time till Day 15 irrespective of the SOV protocol applied (p < 0.05), being non- significantly different between SOV protocols within each time-point (p > 0.05). The number of CL was higher on Day 15 in the bscrFSH group compared to the NIH-FSH-p group (p < 0.05). The number of embryonic structures recovered was higher in the bscrFSH group (p = 0.025), probably as a result of a tendency towards a greater number of follicles developed compared to the NIH-FSH-p group. IFNt and BAX were overexpressed in embryos from the bscrFSH group (p < 0.05), with a fold change of 16 and 1.3, respectively. However, no statistical differences were detected regarding the OCT4, CDX2, BCL2, and BCL2/BAX expression ratio (p > 0.05). In conclusion, including bscrFSH in SOV protocols could be an important alternative by reducing the number of applications and offering an improved ovarian response together with better embryo quality and superior performance in embryo production compared to NIH-FSH-p SOV protocols.


Operant conditioning of H-reflex in freely moving monkeys.
The H-reflex, the electrical analog of the stretch reflex or tendon jerk, is the simplest behavior of the primate CNS. It is subserved by a wholly spinal two-neuron reflex arc. Recent studies show that this reflex can be increased or decreased by operant conditioning, and that such conditioning causes plastic changes in the spinal cord itself. Thus, H-reflex conditioning provides a powerful new model for investigating primate memory traces. The key feature of this model, the conditioning task, originally required animal restraint. This report describes a new tether-based design that allows H-reflex measurement and conditioning without restraint. This design integrates the conditioning task into the life of the freely moving animal.


Estimation and Comparison of Knee Joint Contact Forces During Heel Contact and Heel Rise Deep Squatting.
Increased knee flexion is required for deep squatting in the daily life of the non-western population as well as in many sports activities. The purpose of this study was to estimate as well as to compare knee joint contact forces during heel contact (HC) and heel rise (HR) deep squatting in 10 healthy young Indian participants. Kinematic data were captured using a 12-camera Motion Analysis system. Kinetic data were collected using two Kistler force plates. EMG of 6 lower limb muscles was monitored by Noraxon wireless EMG. OpenSim musculoskeletal model was customized to increase the maximum knee flexion capability of the existing model and knee joint contact forces were estimated. A significant difference in tibiofemoral (p < 0.001) as well as patellofemoral (p = 0.006) knee joint contact force was observed between HC and HR squatting. The resultant maximum tibiofemoral KJCF was 5.9 (± 0.54) times body weight (BW) and 5.3 (± 0.6) BW for the HC and HR, respectively. The resultant maximum patellofemoral KJCF was 7.8 (± 0.57) BW and 7.1 (± 0.73) BW for the HC and HR, respectively. The findings can provide implications for physiotherapists to design rehabilitation exercise protocols, exercise professionals, and the development of high flexion knee implants. The online version contains supplementary material available at 10.1007/s43465-022-00798-y.