Water scarcity hotspots travel downstream due to human interventions in the 20th and 21st century.

Water scarcity is rapidly increasing in many regions. In a novel, multi-model assessment, we examine how human interventions (HI: land use and land cover change, man-made reservoirs and human water use) affected monthly river water availability and water scarcity over the period 1971-2010. Here we show that HI drastically change the critical dimensions of water scarcity, aggravating water scarcity for 8.8% (7.4-16.5%) of the global population but alleviating it for another 8.3% (6.4-15.8%). Positive impacts of HI mostly occur upstream, whereas HI aggravate water scarcity downstream; HI cause water scarcity to travel downstream. Attribution of water scarcity changes to HI components is complex and varies among the hydrological models. Seasonal variation in impacts and dominant HI components is also substantial. A thorough consideration of the spatially and temporally varying interactions among HI components and of uncertainties is therefore crucial for the success of water scarcity adaptation by HI.

Long-term effects of post-ischaemic oestrogen on brain injury in a rat transient forebrain ischaemia model.

BACKGROUND: The current study was conducted to compare the effects of post-treatment with oestrogen on histological and neurological outcomes after short (7-day) and long (28-day) recovery periods in rats subjected to transient forebrain ischaemia. METHODS: Male Sprague-Dawley rats were randomly assigned to one of five groups: vehicle (7-day recovery period), vehicle (28-day recovery period), oestrogen (17ß-estradiol 200 µg/kg, 7-day), oestrogen (17ß-estradiol 200 µg /kg, 28-day), or sham surgical (n = 8 in each group). After forebrain ischaemia was induced with bilateral carotid artery occlusion and haemorrhagic hypotension (mean arterial pressure = 40 mmHg) for 10 min, the brain was reperfused for 7 or 28 days. Either 17ß-estradiol or vehicle was injected intravenously during the initial 2 min of reperfusion. To evaluate histological damage, the number of intact neurons per 1 mm in the hippocampal CA1 subfield was counted at 7 or 28 days after transient forebrain ischaemia. RESULTS: At 7 days after ischaemia, the number of intact neurons in the hippocampal CA1 subfield was significantly greater in the oestrogen group [57.5 (46.5)/mm: median (interquartile range)] than in the vehicle group [10 (19.5) /mm; P = 0.014]. However, there was no difference between groups at 28 days after ischaemia [vehicle: 11 (20)/mm vs. oestrogen: 6 (11)/mm]. The neurological deficit scores in the oestrogen and vehicle groups were not different from the sham group at any point post-ischaemia. CONCLUSION: The current study indicates that post-ischaemic administration of oestrogen provided short-term but not long-term neuroprotective effects in transient forebrain ischaemia in rats.

A MC motif in silkworm Argonaute 1 is indispensible for translation repression.

Small RNA-mediated gene silencing is a fundamental gene regulatory mechanism, which is conserved in many organisms. Argonaute (Ago) family proteins in the RNA-induced silencing complex (RISC) play crucial roles in RNA interference (RNAi) pathways. In the silkworm Bombyx mori, four Ago proteins have been identified, named as Ago1, Ago2, Ago3 and Siwi. Ago2 participates in double-stranded RNA (dsRNA)-induced RNAi, whereas Ago3 and Siwi are involved in the Piwi-interacting RNA (piRNA) pathway. However, there is no experimental evidence concerning silkworm Ago1 (BmAgo1) in the RNAi mechanism. In the present study, we analysed the function of BmAgo1 in the microRNA (miRNA)-mediated RNAi pathway using tethering and miRNA sensor reporter assays. These results clearly demonstrate that BmAgo1 plays an indispensable role in translation repression in silkworm. Moreover, coimmunoprecipitation data indicated that BmAgo1 interacts with BmDcp2, an orthologue of mRNA-decapping enzyme 2 (Dcp2) protein in the Drosophila processing-bodies (P-bodies). Substitutions of two conserved phenylalanines (F522 and F557) by valines in the MC motif strongly impaired the function of BmAgo1 in translation repression and its localization in P-bodies, suggesting that these two amino acid residues in the MC motif of BmAgo1 are prerequisites for mRNA translation repression in B. mori.

Neuroprotective effects of a combination of dexmedetomidine and hypothermia after incomplete cerebral ischemia in rats.

BACKGROUND: Dexmedetomidine and hypothermia are known to reduce neuronal injury following cerebral ischemia. We examined whether a combination of dexmedetomidine and hypothermia reduces brain injury after transient forebrain ischemia in rats to a greater extent than either treatment alone. METHODS: Thirty-eight male Sprague-Dawley rats were anesthetized with fentanyl and nitrous oxide in oxygen. Four groups were tested: group C (saline 1 ml/kg, temporal muscle temperature 37.5 degrees C); group H (saline 1 ml/kg, 35.0 degrees C); group D (dexmedetomidine 100 microg/kg, 37.5 degrees C); and group DH (dexmedetomidine 100 microg/kg, 35.0 degrees C). Dexmedetomidine or saline was administered intraperitoneally 30 min before ischemia. Cerebral ischemia was produced by right carotid artery ligation with hemorrhagic hypotension (mean arterial pressure 40 mmHg) for 20 min. Neurologic outcome was evaluated at 24, 48, and 72 h after ischemia. Histopathology was evaluated in the caudate and hippocampus at 72 h after ischemia. RESULTS: Neurologic outcome was significantly better in the group DH than the group C (P<0.05), whereas it was similar between the group DH and the groups D or H. Survival rate of the hippocampal CA1 neurons was significantly greater in groups D, H, and DH than group C (P<0.05). Histopathologic injury in the caudate section was significantly less in groups H and DH than group C (P<0.05). CONCLUSION: The combination of dexmedetomidine and hypothermia improved short-term neurologic outcome compared with the control group, whereas the combination therapy provided comparable neuroprotection with either of the two therapies alone.

[Complete resection of an advanced mediastinal nonseminomatous germ cell tumor with multiple distant metastases after down-staging by chemotherapy].

A mediastinal nonseminomatous germ cell tumor was completely resected after down-staging by chemotherapy despite the presence of multiple distant metastases. A 22-year-old female was admitted for superior vena cava (SVC) syndrome. Her SVC was obstructed by a large anterior mediastinal tumor; she also exhibited distant metastases on a left rib, in the liver, and multiple in the lung. The blood alpha-fetoprotein (AFP) level was extremely elevated to 57,530 ng/ml. Four courses of BEP therapy [cisplatin (CDDP), bleomycin (BLM), etoposide (VP-16)] and a high dose chemotherapy followed by a peripheral blood stem cell transplantation made the tumor become smaller and effected its down-staging. Residual mediastinal tumor with an intravascular tumor in SVC was completely resected. The SVC was reconstructed by an artificial vessel graft. A mediastinal nonseminomatous germ cell tumor, even though it has multiple distant metastases, can achieve down-staging and complete resection by a chemotherapy based on scientific evidence.

The combined neuroprotective effects of lidocaine and dexmedetomidine after transient forebrain ischemia in rats.

BACKGROUND: We investigated whether coadministration of lidocaine and dexmedetomidine would reduce brain injury following transient forebrain ischemia in rats to a greater extent than either drug alone. METHODS: Adult male Sprague-Dawley rats were anesthetized with halothane to maintain normocapnia and normoxia. Rats received subcutaneous injection of saline 1 ml/kg, lidocaine 10 mg/kg, dexmedetomidine 3 microg/kg, or lidocaine 10 mg/kg plus dexmedetomidine 3 microg/kg. Thirty minutes after the drug injection, forebrain ischemia was induced by hemorrhagic hypotension and occlusion of the bilateral carotid arteries, and was confirmed by isoelectric EEG. At the end of 10-min ischemia, rats were reperfused. The same dose of drugs was administered 3, 24, and 48 h after ischemia. Neurological examination was done at 1, 2, and 7 days after ischemia. Seven days after ischemia, the brain was stained with hematoxylin and eosin. We counted ischemic cells in the CA1 hippocampal region, striatum, and cerebral cortex. We also measured extracellular glutamate and norepinephrine concentration in hippocampal CA1 in the four groups. RESULTS: As compared with saline-treated rats, rats receiving dexmedetomidine plus lidocaine showed less than neurological deficit scores at 2 and 7 days after ischemia, and had less ischemic cells in the CA1 region. However, administration of dexmedetomidine plus lidocaine did not alter the area under the glutamate concentration curve and norepinephrine concentration during ischemia in the CA1 region, compared with saline-treated rats. CONCLUSIONS: Our results suggest coadministration of lidocaine and dexmedetomidine improves the neurological outcome without alteration of glutamate and norepinephrine concentrations during forebrain ischemia in rats.

Proposal for a new clinical entity, IgG4-positive multiorgan lymphoproliferative syndrome: analysis of 64 cases of IgG4-related disorders.

BACKGROUND: Mikulicz's disease (MD) has been considered as one manifestation of Sjögren's syndrome (SS). Recently, it has also been considered as an IgG(4)-related disorder. OBJECTIVE: To determine the differences between IgG(4)-related disorders including MD and SS. METHODS: A study was undertaken to investigate patients with MD and IgG(4)-related disorders registered in Japan and to set up provisional criteria for the new clinical entity IgG(4)-positive multiorgan lymphoproliferative syndrome (IgG(4)+MOLPS). The preliminary diagnostic criteria include raised serum levels of IgG(4) (>135 mg/dl) and infiltration of IgG(4)(+) plasma cells in the tissue (IgG(4)+/IgG+ plasma cells >50%) with fibrosis or sclerosis. The clinical features, laboratory data and pathologies of 64 patients with IgG(4)+MOLPS and 31 patients with typical SS were compared. RESULTS: The incidence of xerostomia, xerophthalmia and arthralgia, rheumatoid factor and antinuclear, antiSS-A/Ro and antiSS-B/La antibodies was significantly lower in patients with IgG(4)+MOLPS than in those with typical SS. Allergic rhinitis and autoimmune pancreatitis were significantly more frequent and total IgG, IgG(2), IgG(4) and IgE levels were significantly increased in IgG(4)+MOLPS. Histological specimens from patients with IgG(4)+MOLPS revealed marked IgG(4)+ plasma cell infiltration. Many patients with IgG(4)+MOLPS had lymphocytic follicle formation, but lymphoepithelial lesions were rare. Few IgG(4)+ cells were seen in the tissue of patients with typical SS. Thirty-eight patients with IgG(4)+MOLPS treated with glucocorticoids showed marked clinical improvement. CONCLUSION: Despite similarities in the involved organs, there are considerable clinical and pathological differences between IgG(4)+MOLPS and SS. Based on the clinical features and good response to glucocorticoids, we propose a new clinical entity: IgG(4)+MOLPS.

Effect of mivazerol, a alpha-agonist, on striatal norepinephrine concentration during transient forebrain ischemia in rats.

BACKGROUND: We have previously reported that mivazerol, a alpha(2)-agonist, possibly provides neuroprotection against transient forebrain ischemia in rats. This study was designed to investigate the ability of mivazerol to attenuate ischemia-induced increase in striatal norepinephrine concentration after transient forebrain ischemia in rats. METHODS: Male Sprague-Dawley rats, anesthetized with halothane, were assigned to one of three groups (n=10 each); control (C, normal saline 1 ml/kg), mivazerol 20 microg/kg (M20), and 40 microg/kg (M40) groups. Monitored variables included temporal muscle temperature (maintained at 37.5+/-0.1 degrees C), electroencephalogram, systolic/diastolic blood pressure, heart rate, arterial blood gases, and blood glucose concentrations. Thirty minutes after subcutaneous drug administration, forebrain ischemia was induced with hemorrhagic hypotension (systolic arterial pressure: 40-50 mmHg) and bilateral carotid artery occlusion for 10 min, and then the brain was reperfused. Norepinephrine concentration in the interstitial fluids in the striatum was analyzed using in vivo microdialysis in combination with high-performance liquid chromatography. RESULTS: Ischemia resulted in a prompt increase in norepinephrine concentrations in the striatum in all groups. However, there were no significant differences in norepinephrine concentrations in the striatum between the three groups at any period. CONCLUSIONS: Our results indicate that mivazerol did not attenuate ischemia-induced increase in striatal norepinephrine concentration. This suggests that the possible neuroprotective property of mivazerol is not related to inhibition of norepinephrine release in the brain.

Anterior pedicle screw fixation for multilevel cervical corpectomy and spinal fusion.

BACKGROUND: Prevention of graft dislodgement in multilevel cervical corpectomy and fusion has been an unresolved problem. Anterior plate fixation has a significant failure rate. External support with a halo-vest is uncomfortable for patients. In the present study, we report a new surgical technique of anterior pedicle screw (APS) fixation for multilevel cervical corpectomy and spinal fusion, and describe the safety and utility of the system. METHOD: After cervical corpectomy, the pedicles on the right side were visualised under oblique fluoroscopy. Guide wires were inserted into the pedicles from the inner wall of the excavated vertebral body until they were hidden in the pedicles. After a fibula autograft was placed, the graft was penetrated in the reverse direction by the guide wires. After drilling and tapping, cannulated screws were inserted into the pedicles through the grafted fibula along the guide wires. FINDINGS: In 9 patients with cervical myelopathy, the surgery was accomplished with a fibula autograft using APS fixation. A total of 22 APSs were inserted, and 21 screws were placed precisely in the pedicles. There were no neurovascular complications. Patients were allowed to ambulate without a halo-vest on the second day after the surgery. Post-operatively, no dislodgement of the grated fibula occurred, and all patients improved neurologically. CONCLUSIONS: The insertion of APSs is feasible and safe. APS fixation enables us to obtain rigid fixation anteriorly, and we propose that APS fixation is an attractive option for multilevel cervical corpectomy and fusion.

Successful treatment of amegakaryocytic thrombocytopenia with anti-CD20 antibody (rituximab) in a patient with systemic lupus erythematosus.

Amegakaryocytic thrombocytopenia is an extremely rare disorder in systemic lupus erythematosus, and its mechanism and treatment are still largely unknown. We describe a 42-year-old woman with systemic lupus erythematosus who presented various clinical manifestations of life-threatening amegakaryocytic thrombocytopenia (10,000 platelets/mm3 with a marked decrease of megakaryocytes in the bone marrow), proteinuria, psychosis, refractory chylothorax, ascites, and type II diabetes caused by the anti-insulin receptor autoantibody. She was initially treated with prednisolone (25-50 mg/day) and cyclosporine A (200 mg/day) without any improvement in severe thrombocytopenia. However, her clinical symptoms, including platelet counts, dramatically improved, with a concurrent decrease in the anti-c-Mpl antibody, an autoantibody against the thrombopoietin receptor, after a subsequent treatment with rituximab (375 mg/m2 intravenously, weekly, for two consecutive weeks). Our case suggested that amegakaryocytic thrombocytopenia in patients with systemic lupus erythematosus might be mediated by the anti-c-Mpl antibody and could be treated with rituximab through elimination of pathogenic B cells producing autoimmune antibodies.

Clonality analysis of lymphoproliferative disorders in patients with Sjögren's syndrome.

The aim of this study was to clarify the nature of the clonal lymphocyte infiltration in Sjögren's syndrome (SS) patients associated with lymphoproliferative disorders. We examined B cell clonality in lymphoproliferative tissues from six primary SS patients associated with lymphoproliferative disorders or lymphoma by cloning and sequencing of the gene rearrangement of the immunoglobulin heavy chain complementarity determining region 3 (IgVH-CDR3). Three patients with sequential observation showed progressional clonal expansion with the presence of the same subclone in different tissues during the course of disease. Among them, one patient developed mucosa-associated lymphoid tissue (MALT) lymphoma in glandular parotid. The other three SS patients concomitant with malignant B cells lymphomas showed different clonal expansion of B cells between nodal sites and salivary glands. The cloanality analysis indicated that monoclonal B cell population could spread from one glandular site to another site during the course of SS, suggesting that the malignant clone may arise from the general abnormal microenvironment, not restricted to the glandular tissue, in some SS patients.

Neuroprotective effect of mivazerol, an alpha 2-agonist, after transient forebrain ischemia in rats.

BACKGROUND: We examined whether mivazerol, an alpha2-agonist, had neuroprotective effects after transient forebrain ischemia in rats. METHODS: Male Sprague-Dawley rats, anesthetized with halothane, were assigned to one of four groups (n=10 each): control (C, normal saline) and mivazerol 10 microg/kg (M10), 20 microg/kg (M20) and 40 microg/kg (M40) groups. Thirty minutes after drug administration, forebrain ischemia was induced with hemorrhagic hypotension and bilateral carotid artery occlusion for 10 min, and then the brain was reperfused. The neurologic outcome was evaluated 24 h, 48 h and 7 days after ischemia, followed by histologic evaluation. RESULTS: The survival rate during 7 days was significantly lower in group M40 than in groups M10 and M20 (P<0.05). The neurologic outcome was significantly better in groups M10 and M20 than in group M40 7 days after ischemia (P<0.05). The number of intact neurons in hippocampal CA1 was significantly greater in group M20 than in the other groups (P<0.05). Neuronal injury in the neocortex was significantly less in group M20 than in groups C and M40 (P<0.05). CONCLUSIONS: Our results suggest that mivazerol, up to 20 microg/kg, provides neuroprotective effects, whereas 40 microg/kg may exaggerate neuronal injury after transient forebrain ischemia in rats.

Quantitative analysis of amoA mRNA expression as a new biomarker of ammonia oxidation activities in a complex microbial community.

AIMS: To quantitatively analyse the changes to amoA mRNA (ammonia mono-oxygenase encoding mRNA) profiles in response to a change in ammonia oxidation activity in a complex microbial community. METHODS AND RESULTS: The amoA mRNA levels in both a batch-mode incubation and a continuously fed nitrification reactor were determined by real-time reverse transcription-PCR analysis. The amoA mRNA level changed rapidly in response to the change in environmental conditions which affect ammonia oxidation activity. CONCLUSION: An increase in amoA mRNA level can be detected within 1-2 h in response to an initiation of cell activity whereas a decrease in amoA mRNA level is detected within 24 h in response to a cessation of activity. SIGNIFICANCE AND IMPACT OF THE STUDY: amoA mRNA, which shows sensitive response to ammonia oxidation activity, can be used as a biomarker of ammonia oxidation activity in wastewater treatment processes where many bacterial species exist.

Granulocytic sarcoma of megakaryoblastic differentiation in the lymph nodes terminating as acute megakaryoblastic leukemia in a case of chronic idiopathic myelofibrosis persisting for 16 years.

A 43-yr-old Japanese woman presented with mild anemia, leukocytosis and splenomegaly in May 1984. Splenomegaly and anemia gradually progressed. Sixteen years later, in October 2000, she developed inguinal lymphadenopathy. Biopsy of the lymph node revealed infiltration of blasts, megakaryocytes, fibroblasts and myeloid cells. Large blasts with basophilic cytoplasm with cytoplasmic projections appeared in the peripheral blood. These blasts were negative in peroxidase stain, positive in acid phosphatase and weakly positive in periodic acid-Schiff stain. Immunohistochemical staining with monoclonal antibodies revealed that these blasts were positive with anti-CD41 (glycoprotein IIb/IIIa) and negative with other monoclonal antibodies. So diagnosis of granulocytic sarcoma in megakaryoblastic transformation from chronic idiopathic myelofibrosis was made. A cytogenetic study revealed that bone marrow cells were 46,XX del(13)(q?) initially and additional abnormalities including der(5,5,11)(q11;q13)ins(5;?)(q11;?) were found when she developed megakaryoblastic transformation. Granulocytic sarcoma of megakaryoblastic transformation from chronic idiopathic myelofibrosis is a rare event. Immunophenotyping with monoclonal antibody for CD41(glycoprotein IIb/IIIa) confirmed the diagnosis.

[A study on cervical reflex induced by click stimuli in cats].

UNLABELLED: The effects of click stimuli on the cervical muscle have been wildly studied, but no information is available on what reaction click stimuli elicit from the cervical cord. We studied the effects of click stimuli on the cervical cord in cats. PURPOSE: To determine the response of the cervical cord to click stimuli in cats. MATERIALS AND METHODS: Subjects were ten adult cats confirmed to have normal tympanic membranes. Cats were placed on artificial ventilation by tracheal incision. Auditory brainstem response (ABR) of both ears was measured to determine its threshold. Following the cervical incision, the dorsal vertebrae were removed, the cervical cord was exposed at C3 to C6, and bipolar needle electrodes were inserted. The reference electrode was attached to the forehead. Click stimuli were presented using 1-20 Hz clicks. RESULTS: Responses peaking at 4.89-5.10 ms were induced by click stimuli of 105 dBSPL (1 Hz) at C3. Latencies tended to be prolonged with decreasing sound pressure. No response was confirmed at of C4 to C6. The responses to clicks of 20 Hz or more disappeared when 100 responses were summed. After the experiment, we confirmed that accessory nerves showed a response to electrical stimuli applied by bipolar needle electrodes. The cervical cord was removed to make sure that the electrode had been passed into the spinal nucleus of the accessory nerve. DISCUSSION: Spinal nuclei of accessory nerves exist at C3 to C5 of the cervical cord, and are associated with the movement of the sternocleidomastoid muscle at C3 in particular. Click stimuli are reported to affect the sternocleidomastoid muscle. The results of our study appear to reflect the response of the spinal nucleus of the accessory nerve to click stimuli. The fact that responses to clicks of 20 Hz or more disappeared when 100 responses were summed suggests that the response was induced via a pathway other than the auditory pathway.

Investigation of coronary artery bypass grafting for a patient with myelodysplastic syndrome.

A 79-year-old male with unstable angina, who had myelodysplastic syndrome (MDS), was treated with coronary artery bypass grafting (CABG). MDS causes refractory anemia accompanied by various degrees of granulocytopenia and thrombocytopenia. Pancytopenia caused by MDS may complicate patients with major infections and bleeding during cardiac surgery. There were very few patients with MDS who had undergone open-heart surgery. Three case studies, including this study, had reported successful cases of CABG in patients with MDS and the analogous diseases of MDS. We used granulocyte colony-stimulating factor (G-CSF), red blood cells (RBCs) and platelets transfusions in peri-operative state. We did not need a large amount of transfusion of RBCs and platelets in intra-operative and postoperative states. We had prevented major bleeding and severe wound infections in the acute postoperative state.

Oxidative transformation of arylmethyl bromides and alcohols with a combination of mesoporous silica FSM-16 and alkali iodides under photoirradiation.

[reaction: see text]. A mesoporous silica FSM-16 was found to be a selective and recyclable promoter for the oxidative dehalogenation of arylmethyl bromides to provide the corresponding alcohols and for the oxidation of arylmethyl alcohols to provide the corresponding aldehydes with a combination of alkali iodides and solvents under photoirradiation conditions.

T-Cell type acute lymphoblastic leukemia following cyclosporin A therapy for aplastic anemia.

Cyclosporin A (CsA) is used to prevent rejection in transplantation and to treat autoimmune and hematologic diseases such as aplastic anemia. However, the tumor growth-promoting effect of CsA remains controversial. We report the case of a 24-year-old man who developed acute lymphoblastic leukemia of precursor-T-cell origin after 75 months of treatment with CsA for aplastic anemia. The surface antigen phenotype of his leukemic cells was CD2+, CD3+, CD5+, CD7+, CD4-, CD8-, CD10-, CD20-, CD34-, CD41-, and CD56-. Southern blot analysis revealed a monoclonal rearrangement of T-cell receptor-Jgamma nongermline fragments in HindIII digestion.

[A case of Sjögren's syndrome with dermatomyositis who died of rapidly progressive interstitial pneumonia].

We report a case of 55 year-old woman with six year history of Sjögren's syndrome developed fatal rapidly progressive interstitial pneumonia. She had been well until February 1999. She developed swelling and erythematous lesions in the cheek and hands in spring 1999. She was admitted to our hospital for investigations of skin lesions in May 1999. Physical examination on admission revealed small hemorrhagic lesions in the nailfold. Serum CK level was slightly elevated. Electromyogram and MRI suggested mild myositis in the proximal upper extremities. She was suspected to have dermatomyositis along with Sjögren's syndrome. Prednisolone 10 mg/day had been given for her skin problems since March 1999. Suddenly, dyspnea on exertion was appeared on 34th day of admission. Chest X-ray film showed an acute worsening of interstitial pneumonia. Methylprednisolone pulse therapy (1000 mg for 3 days) and cyclophosphamide pulse therapy (500 mg for a day) were started, and she was subsequently treated with 60 mg/day of prednisolone and 250 mg/day of Cyclosporin A. However, interstitial pneumonia did not respond to the treatment, and pneumomediastinum and pneumothorax have developed. She died of respiratory failure on 55th day. We consider that most likely explanation for fatal interstitial pneumonia is concomitantly occurred dermatomyositis.