Spatiotemporal and seasonal transmission dynamics of Schistosoma haematobium and snail infectivity in Ase River catchment, Delta State, Nigeria.

Bulinus are intermediate snail hosts of Schistosoma haematobium. Despite their vectorial role, the transmission dynamics and infectivity of these intermediate snail hosts remain understudied in the Ase River. This longitudinal study evaluated the geospatial and seasonal transmission patterns and infectivity of three S. haematobium vectors between November 2020 and October 2022 in the Ase River catchment, Delta State, Nigeria. Eleven (11) geospatial water contact coordinates were mapped for monthly spatiotemporal collection of Bulinus species along the Ase River and its catchment, for two years. Snail sampling was performed for 45 min at each study site using scooping/hand-picking techniques and subsequently counted, identified and recorded. Snails of the Bulinus genus were individually placed in a beaker containing distilled water and exposed to light to shed cercariae which were identified to be human schistosome type. The number of infected snails for each month and season was also documented to analyze the spatiotemporal and seasonal transmission dynamics of infectivity. Out of the 2345 Bulinus snails collected, a total of 41.45% were found to be infected with S. haematobium. The monthly infectivity of Bulinus snails varied significantly (P < 0.05) throughout the study period (P = < 0.0001; F = 23.11; df = 11). Further analysis showed a strong significant association (χ2 = 23.57; df = 11; p = 0.015) between the study years. The Principal Component Analysis (PCA) results suggest that Bulinus infectivity within the Ase River catchment area was primarily associated with the months of February and January. B. truncatus consistently had the highest transmission potential, followed by B. globosus and B. senegalensis. ANOVA confirms that the monthly/study site infectivity and transmission potential in B. truncates, B. globosus and S. senegalensis were statistically, significant (P < 0.05). These results demonstrated a clear distinction in the patterns and relationships between the different months in terms of snail infectivity and seasonal transmission potential. This understanding will help in the continuous monitoring and targeted interventions to control schistosomiasis transmission in Ase River.

An in vivo screening system to identify tumorigenic genes.

Screening for oncogenes has mostly been performed by in vitro transformation assays. However, some oncogenes might not exhibit their transforming activities in vitro unless putative essential factors from in vivo microenvironments are adequately supplied. Here, we have developed an in vivo screening system that evaluates the tumorigenicity of target genes. This system uses a retroviral high-efficiency gene transfer technique, a large collection of human cDNA clones corresponding to ~70% of human genes and a luciferase-expressing immortalized mouse mammary epithelial cell line (NMuMG-luc). From 845 genes that were highly expressed in human breast cancer cell lines, we focused on 205 genes encoding membrane proteins and/or kinases as that had the greater possibility of being oncogenes or drug targets. The 205 genes were divided into five subgroups, each containing 34-43 genes, and then introduced them into NMuMG-luc cells. These cells were subcutaneously injected into nude mice and monitored for tumor development by in vivo imaging. Tumors were observed in three subgroups. Using DNA microarray analyses and individual tumorigenic assays, we found that three genes, ADORA2B, PRKACB and LPAR3, were tumorigenic. ADORA2B and LPAR3 encode G-protein-coupled receptors and PRKACB encodes a protein kinase A catalytic subunit. Cells overexpressing ADORA2B, LPAR3 or PRKACB did not show transforming phenotypes in vitro, suggesting that transformation by these genes requires in vivo microenvironments. In addition, several clinical data sets, including one for breast cancer, showed that the expression of these genes correlated with lower overall survival rate.

Recovery After Critical Illness Polyneuropathy in a Patient With Orthotopic Liver Transplantation: A Case Report.

After liver transplantation, some patients show neuromuscular abnormalities. A 43-year-old man with liver cirrhosis due to hepatitis C virus underwent living-donor liver transplantation. He developed severe neuromuscular dysfunction after sepsis, and acute respiratory distress syndrome. After the inflammatory reaction gradually improved, we observed bilateral weakness of the extremities and foot drop. Electrophysiological studies indicated primary axonal degeneration of peripheral motor and sensory fibers without inflammation. Critical illness polyneuropathy was diagnosed. During follow-up, complaints gradually recovered with rehabilitation by approximately 1 year later. Based on this case, we suggest that paralysis should be evaluated for critical illness polyneuropathy in patients with unexplained muscle weakness.

Spectrum of clinical and genetic features of patients with inherited platelet disorder with suspected predisposition to hematological malignancies: a nationwide survey in Japan.

BACKGROUND: Inherited thrombocytopenia (IT) contains several forms of familial thrombocytopenia and some of them have propensity to hematological malignancies. The etiological and genetic features of this heterogeneous syndrome have not yet been elucidated. PATIENTS AND METHODS: We conducted a nationwide survey to collect clinical information and samples from patients with familial thrombocytopenia and/or hematological malignancies in order to obtain a comprehensive understanding of IT. RESULTS: Among the 43 pedigrees with clinical samples, RUNX1 mutations were identified in 8 pedigrees (18.6%). While MYH9 and ANKRD26 mutations were identified in 2 and 1 pedigrees, respectively, no gene mutations were detected in the remaining 32 pedigrees from a panel of previously reported pathogenetic mutations. Clinical data were comparable between FPD/AML and non-FPD/AML probands. CONCLUSIONS: Our study clarified that it is unexpectedly difficult to diagnose FPD/AML based on clinical information alone, and thus, genetic testing is strongly recommended. Our survey also identified some pedigrees with a strong family history of myelodysplastic syndromes of unknown origin. Additionally, there were 14 pedigrees in which three or more members were affected by immune thrombocytopenia (ITP), and a computer-aided simulation suggested that such a distribution almost never happens by coincidence, which implicates a genetic predisposition to ITP.

Impact of body mass index on postoperative complications and long-term survival in patients with esophageal squamous cell cancer.

Undernutrition and cachexia have been suggested to be risk factors for postoperative complications and survival in cancer patients. The aim of this study was to investigate whether body mass index (BMI) is related to the short-term and long-term outcomes in patients who undergo an esophagectomy for the resection of esophageal squamous cell cancer (ESCC). Three hundred forty patients who underwent an esophagectomy for the resection of ESCC between 2003 and 2008 were retrospectively reviewed. The patients were divided into two groups: an L-BMI group characterized by a BMI < 18.5 kg/m(2) and an N-BMI group characterized by a BMI ≥ 18.5 kg/m(2). Clinical and pathological outcome were compared between groups. The study included 40 patients in the L-BMI group and 300 patients in the N-BMI group. A clinicopathological assessment showed that nodal involvement was seen more frequently in the L-BMI group (P = 0.016). Pulmonary complications seemed to occur more frequently in the L-BMI group (P = 0.006). The 5-year overall survival rate was higher in the N-BMI group (63.6%) than in the L-BMI group (32.3%) (P < 0.001). The 5-year disease-free survival rate was also higher in the N-BMI group (58.0%) than in the L-BMI group (33.6%) (P = 0.001). In multivariate analysis, the BMI (hazard ratio, 2.154; 95% CI, 1.349-3.440, P = 0.001) was found to be an independent prognostic factor for overall survival. Our data suggested that a lower BMI not only increased pulmonary complications but also impaired overall and disease-free survival after an esophagectomy for the resection of ESCC.

Function of insulin in snail brain in associative learning.

Insulin is well known as a hormone regulating glucose homeostasis across phyla. Although there are insulin-independent mechanisms for glucose uptake in the mammalian brain, which had contributed to a perception of the brain as an insulin-insensitive organ for decades, the finding of insulin and its receptors in the brain revolutionized the concept of insulin signaling in the brain. However, insulin's role in brain functions, such as cognition, attention, and memory, remains unknown. Studies using invertebrates with their open blood-vascular system have the promise of promoting a better understanding of the role played by insulin in mediating/modulating cognitive functions. In this review, the relationship between insulin and its impact on long-term memory (LTM) is discussed particularly in snails. The pond snail Lymnaea stagnalis has the ability to undergo conditioned taste aversion (CTA), that is, it associatively learns and forms LTM not to respond with a feeding response to a food that normally elicits a robust feeding response. We show that molluscan insulin-related peptides are up-regulated in snails exhibiting CTA-LTM and play a key role in the causal neural basis of CTA-LTM. We also survey the relevant literature of the roles played by insulin in learning and memory in other phyla.

Can Spirulina maxima reduce the mutagenic potential of sibutramine?

The worldwide obesity pandemic requires the use of anti-obesity drugs. Sibutramine is an anti-obesity drug that has been used worldwide but is indiscriminately consumed in Brazil. Several studies have demonstrated that sibutramine promotes weight loss and weight maintenance, but several side effects have been associated with its systematic consumption. For this reason, sibutramine was withdrawn from the European and American markets, but still remains legal for use in Brazil. Studies have shown that a 5-10% reduction in body weight results in outstanding health benefits for obese patients. However, in order to promote significant weight loss, it is necessary to use sibutramine for at least 2 years. This long-term exposure has carcinogenic potential, as sibutramine causes DNA damage. Thus, this study evaluated the in vivo mutagenic potential of sibutramine alone (5, 7, 10, 15, and 20 mg/kg) and in association with Spirulina maxima (150 and 300 mg/kg), a cyanobacterium with antioxidant potential, using the polychromatic erythrocyte micronucleus test. Our results reinforced the mutagenic potential of sibutramine alone, which showed a time-dependent action. Combinatory treatments with S. maxima were not able to reduce the genotoxicity of sibutramine. These results were confirmed in vitro with the cytokinesis-blocked micronucleus test. In conclusion, our data showed that new alternative anti-obesity treatments are needed since the consumption of sibutramine can increase the risk of cancer in overweight patients.

Mutagenic potential of Cordia ecalyculata alone and in association with Spirulina maxima for their evaluation as candidate anti-obesity drugs.

Obesity is one of the most important nutritional disorders, and can be currently considered as an epidemic. Although there are few weight reduction drugs available on the market, some new drug candidates have been proposed, including Cordia ecalyculata, a Brazilian plant with anorectic properties, and Spirulina maxima, a cyanobacterium with antioxidant and anti-genotoxic activity. In this study, we evaluated the mutagenic potential of C. ecalyculata at doses of 150, 300, and 500 mg/kg alone and in association with S. maxima at doses of 75, 150, and 250 mg/kg, respectively, through an in vivo micronucleus test, using mice of both sexes, and an in vitro micronucleus test and comet assay, using human peripheral blood. For all tests, cyclophosphamide was used as a positive control. The results showed that treatment of 300 mg/kg C. ecalyculata and the combination treatment of 500 mg/kg C. ecalyculata with 250 mg/kg S. maxima resulted in anorectic effects. The mutagenic tests did not reveal any clastogenic or genotoxic activity for any treatment, indicating that these candidates could be marketed as weight-reduction drugs. Moreover, the drugs contain chemo-preventive substances that can protect against tumorigenesis, which has been associated with obesity.

Impaired hematopoietic differentiation of RUNX1-mutated induced pluripotent stem cells derived from FPD/AML patients.

Somatic mutation of RUNX1 is implicated in various hematological malignancies, including myelodysplastic syndrome and acute myeloid leukemia (AML), and previous studies using mouse models disclosed its critical roles in hematopoiesis. However, the role of RUNX1 in human hematopoiesis has never been tested in experimental settings. Familial platelet disorder (FPD)/AML is an autosomal dominant disorder caused by germline mutation of RUNX1, marked by thrombocytopenia and propensity to acute leukemia. To investigate the physiological function of RUNX1 in human hematopoiesis and pathophysiology of FPD/AML, we derived induced pluripotent stem cells (iPSCs) from three distinct FPD/AML pedigrees (FPD-iPSCs) and examined their defects in hematopoietic differentiation. By in vitro differentiation assays, FPD-iPSCs were clearly defective in the emergence of hematopoietic progenitors and differentiation of megakaryocytes, and overexpression of wild-type (WT)-RUNX1 reversed most of these phenotypes. We further demonstrated that overexpression of mutant-RUNX1 in WT-iPSCs did not recapitulate the phenotype of FPD-iPSCs, showing that the mutations were of loss-of-function type. Taken together, this study demonstrated that haploinsufficient RUNX1 allele imposed cell-intrinsic defects on hematopoietic differentiation in human experimental settings and revealed differential impacts of RUNX1 dosage on human and murine megakaryopoiesis. FPD-iPSCs will be a useful tool to investigate mutant RUNX1-mediated molecular processes in hematopoiesis and leukemogenesis.

Clinicopathological significance of laminin-5γ2 chain expression in superficial esophageal cancer.

The glycoprotein laminin 5γ2 chain (LN-5γ2) has recently become a focus of increased interest and investigation as a marker of invasion in gastrointestinal malignancies. We investigated the significance of LN-5γ2 expression as a prognostic factor in superficial esophageal cancer. The study population consisted of 87 patients who had undergone a transthoracic esophagectomy and three-field lymphadenectomy for the treatment of superficial esophageal cancer at Tokai University Hospital. Formalin-fixed, paraffin-embedded sections of the resected specimens were examined using immunohistochemical staining and hematoxylin and eosin staining to assess the correlations between the LN-5γ2 expression pattern and the clinicopathological factors (age, sex, T-factor, N-factor, ly-factor, v-factor, degree of differentiation, infiltrative growth pattern, tumor node metastasis classification of malignant tumors [TNM] stage, etc.) and the patient outcome. The expression pattern of LN-5γ2 was classified into an extracellular type (E type), characterized by the staining of extracellular matrix such as the basement membrane and the stroma (31 cases, 35.6%), and a cytoplasmic type (C type), characterized by the staining of the cytoplasm in the cancer cells (56 cases, 64.6%). The expression pattern was not correlated with any of the clinicopathological factors that were assessed. However, univariate analyses of the survival analysis data showed that the N-factor (P = 0.011), TNM stage (P = 0.011), and LN-5γ2 C type (P = 0.017) were prognostic factors. A multivariate analysis revealed that the N-factor (P = 0.049) and LN-5γ2 C type (P = 0.048) were prognostic factors. In the survival analysis, a univariate analysis of the 75 T1b cases also showed that the N-factor (P = 0.048), TNM stage (P = 0.048), and LN-5γ2 C type (P = 0.029) were prognostic factors, while a multivariate analysis showed that the LN-5γ2 C type (P = 0.035) was a prognostic factor. The C type expression of LN-5γ2, i.e. confined to the cytoplasm, was correlated with an unfavorable outcome among the patients with superficial esophageal cancer in the present series. Observation of the LN-5γ2 expression pattern may be useful for the diagnosis of highly malignant tumors.

Radiation therapy for extramammary Paget's disease: treatment outcomes and prognostic factors.

BACKGROUND: Extramammary Paget's disease (EMPD) is a relatively rare malignancy, and there are few reports related to radiation therapy. In the present study, we investigated the outcome of radiation therapy for EMPD. PATIENTS AND METHODS: Forty-one patients with EMPD in the genitalia underwent radiation therapy with curative intent. Fifteen patients had regional lymph node metastases before radiation therapy, but none had distant metastasis. Total doses of 45-80.2 Gy (median, 60 Gy) were delivered to tumor sites in 23-43 fractions (median, 33 fractions). RESULTS: At a median follow-up period of 41 months, 16 patients had developed recurrences, including 5 with local progression within the radiation field and 12 with lymph node or/and distant metastases outside the radiation field. The local progression-free and disease-free rates were 88% and 55% at 3 years, and 82% and 46% at 5 years, respectively. Nine patients died at 6-73 months after irradiation; the causes of death were tumor progression in five patients, infectious pneumonia in two, renal failure in one and old age in one. The overall and cause-specific survival rates were 93% and 96% at 3 years, and 68% and 84% at 5 years, respectively. Tumor invasion into the dermis and regional lymph node metastasis were significant prognostic factors for both distant metastasis and survival. No therapy-related toxicities of grade ≥3 were observed. CONCLUSIONS: Radiation therapy is safe and effective for patients with EMPD. It appeared to contribute to prolonged survival owing to good tumor control, and to be a promising curative treatment option.

Mitochondrial swelling and incipient outer membrane rupture in preapoptotic and apoptotic cells.

Outer mitochondrial membrane (OMM) rupture was first noted in isolated mitochondria in which the inner mitochondrial membrane (IMM) had lost its selective permeability. This phenomenon referred to as mitochondrial permeability transition (MPT) refers to a permeabilized inner membrane that originates a large swelling in the mitochondrial matrix, which distends the outer membrane until it ruptures. Here, we have expanded previous electron microscopic observations that in apoptotic cells, OMM rupture is not caused by a membrane stretching promoted by a markedly swollen matrix. It is shown that the widths of the ruptured regions of the OMM vary from 6 to 250 nm. Independent of the perforation size, herniation of the mitochondrial matrix appeared to have resulted in pushing the IMM through the perforation. A large, long focal herniation of the mitochondrial matrix, covered with the IMM, was associated with a rupture of the OMM that was as small as 6 nm. Contextually, the collapse of the selective permeability of the IMM may precede or follow the release of the mitochondrial proteins of the intermembrane space into the cytoplasm. When the MPT is a late event, exit of the intermembrane space proteins to the cytoplasm is unimpeded and occurs through channels that transverse the outer membrane, because so far, the inner membrane is impermeable. No channel within the outer membrane can expose to the cytoplasm a permeable inner membrane, because it would serve as a conduit for local herniation of the mitochondrial matrix.

Mathematical analysis of the honeybee waggle dance.

A honeybee informs her nestmates of the location of a flower by doing a waggle dance. The waggle dance encodes both the direction of and distance to the flower from the hive. To reveal how the waggle dance benefits the colony, we created a Markov model of bee foraging behavior and performed simulation experiments by incorporating the biological parameters that we obtained from our own observations of real bees as well as from the literature. When two feeders were each placed 400 m away from the hive in different directions, a virtual colony in which honeybees danced and correctly transferred information (a normal, real bee colony) made significantly greater numbers of successful visits to the feeders compared to a colony with inaccurate information transfer. Howerer, when five feeders were each located 400 m from the hive, the inaccurate information transfer colony performed better than the normal colony. These results suggest that dancing's ability to communicate accurate information depends on the number of feeders. Furthermore, because non-dancing colonies always made significantly fewer visits than those two colonies, we concluded that dancing behavior is beneficial for hives' ability to visit food sources.

GABAergic effects on the slow oscillatory neural activities in the procerebrum of Limax valentianus. Short communication.

We examined GABAergic modulation on "slow" oscillation (<1.0 Hz) of the procerebrum in the terrestrial mollusk, Limax valentianus. Short application of GABA-receptor agonists slightly increased the frequency of a periodic oscillation in the procerebrum, whereas persistent application decreased it. GABA-receptor antagonists decreased the oscillatory frequency. The GABA-like immunoreactivities were found in the neuropil and the cell body layers of the procerebrum. Because GABAergic inhibition is known to be essential for the generation of "fast" synchronous neuronal oscillation in the CNSs in othre many animals, our present findings are first evidence suggesting that GABA modulates 'slow' oscillation in the CNS.

Analysis of DNA endoreplication in the brain neurons in the terrestrial slug, Limax valentianus.

DNA endoreplication is the DNA synthesis without cell division, resulting in the generation of a nucleus containing a larger amount of genomic DNA compared to a normal diploid genome. There are many such giant neurons in the molluscan brain that are generated as a result of repeated endoreplication. However, it has been controversial whether the endoreplication is the whole genome replication (polyploidy) or the local amplification of the genes that are necessary for the neuron's function (polyteny/polysomy). Here in this study, we investigated these two possibilities by (1) immunohistochemical analysis of the distribution of 5'-bromodeoxyuridine incorporated into the nuclei of the brain neurons, and by (2) quantitative genomic PCR directed to two different genes expressed in specific brain regions. Our data supported the view that the DNA endoreplication is the whole genome replication rather than the local amplification of a specific genomic region.

Insulin and memory in Lymnaea.

The pond snail, Lymnaea stagnalis, is capable of learning conditioned taste aversion (CTA) and consolidating this CTA into long-term memory (LTM). The DNA microarray experiments showed that some of molluscan insulin-related peptides (MIPs) were up-regulated in snails exhibiting CTA-LTM. On the other hand, the electrophysiological experiments showed that application of secretions from the MIPs-containing cells evoked long-term potentiation (LTP) at the synapses between the cerebral giant cell (a key interneuron for CTA) and the B1 motoneuron (a buccal motoneuron). We thus hypothesized that MIPs and MIP receptors play an important role at the synapses, probably underlying the CTA-LTM consolidation process. To examine this hypothesis, we applied the antibody, which recognizes the binding site of mammalian insulin receptors and is thought to cross-react MIP receptors, to the Lymnaea CNS. Our present data showed that an application of the antibody for insulin receptors to the isolated CNS blocked LTP, and that an injection of the antibody into the Lymnaea abdominal cavity inhibited LTM consolidation, but not CTA formation.

N-Ion-implanted TiO2 photoanodes in quantum dot-sensitized solar cells.

Hierarchical nanostructured titanium dioxide (TiO(2)) clumps were fabricated using electrostatic spray with subsequent nitrogen-ion doping by an ion-implantation technique for improvement of energy conversion efficiency for quantum dot-sensitized solar cells (QDSCs). CdSe quantum dots were directly assembled on the produced N-ion-implanted TiO(2) photoanodes by chemical bath deposition, and their photovoltaic performance was evaluated in a polysulfide electrolyte with a Pt counter electrode. We found that the photovoltaic performance of TiO(2) electrodes was improved by nearly 145% upon N-ion implantation. The efficiency improvement seems to be due to (1) the enhancement of electron transport through the TiO(2) layer by inter-particle necking of primary TiO(2) particles and (2) an increase in the recombination resistance at TiO(2)/QD/electrolyte interfaces by healing the surface states or managing the oxygen vacancies upon N-ion doping. Therefore, N-ion-doped photoanodes offer a viable pathway to develop more efficient QD or dye-sensitized solar cells.