Geographical distribution of close kin in southern right whales on feeding grounds.

This study investigated the close kinship structure of southern right whales on feeding grounds during austral summer seasons. The study was based on biopsy samples of 171 individual whales, which were genotyped with 14 microsatellite DNA loci. Kinship was investigated by using the LOD (Log Odds) score, a relatedness index for a pair of genotypes. Based on a cut-off point of LODPO > 6, which was chosen to balance false positives and negatives, a total of 28 dyads were inferred. Among these, 25 were classified as parent-offspring pairs. Additional genetic (mitochondrial DNA haplotypes) and biological (estimated body length, sex) data were used to provide additional information on the inferred close kin pairs. The elapsed time between sampling varied from 0 (close kin detected in the same austral summer season) to 17 years. All the kin pairs occurred within the Antarctic Indo sector (85°-135°E) and no pair occurred between whales within and outside of this sector. Six pairs were between individuals in high (Antarctic) and lower latitudes. Results of the present analysis on kinship are consistent with the views that whales in the Indo sector of the Antarctic are related with the breeding ground in Southwest Australia, and that whales from this population can occupy different feeding grounds. The present study has the potential to contribute to the conservation of the southern right whales through the monitoring of important population parameters such as population sizes and growth rate, in addition to assist the interpretation of stock structure derived from standard population genetic analyses.

Systemic Amyloid A Amyloidosis Secondary to Xanthogranulomatous Pyelonephritis.

The combination of systemic amyloid A (AA) amyloidosis and xanthogranulomatous pyelonephritis (XGP) resulting from a chronic urinary tract infection is extremely rare. We herein report a case of systemic AA amyloidosis secondary to XGP for which clinical remission developed after nephrectomy. To our knowledge, this is the first case report describing the clinical improvement of systemic AA amyloidosis secondary to XGP after nephrectomy in Japan. Clinicians should be aware of this uncommon combination and search for amyloid depositions in cases of XGP.

Thrombotic microangiopathy in a patient with anti-signal recognition particle antibody-positive immune-mediated necrotizing myopathy.

We describe the case of a 61-year-old woman with anti-signal recognition particle (SRP) antibody-positive immune-mediated necrotizing myopathy (IMNM) who exhibited biopsy-confirmed thrombotic microangiopathy (TMA). The patient developed proximal-dominant muscle weakness and was diagnosed with anti-SRP antibody-positive IMNM based on muscle biopsy results and serological examination. A high-dose corticosteroid prescription was initiated, followed by intravenous methylprednisolone and intravenous immunoglobulin therapy (IVIg). The patient showed IVIg-induced hemolytic anemia with preserved ADAMTS13 activity. Transient oral tacrolimus administration was initiated. Approximately 8 weeks after admission, the serum creatinine levels gradually increased. Renal histological examination revealed TMA, including ischemic changes in the renal tubules, stenosis, and occlusion of the interlobular arteries with fibrinoid necrosis of the afferent arteriolar walls. The arteriolar walls demonstrated an accumulation of C1q and C3c. Myofiber damage in patients with IMNM accounts for the activation of the classical pathway of the complement cascade in the sarcolemma due to antibody deposition. Additionally, a membrane attack complex is observed on capillaries in the muscle tissues of patients with anti-SRP antibody-positive IMNM. Although drug-induced pathomechanisms, such as IVIg and tacrolimus, can trigger the development of TMA, we suggest that the presence of serum anti-SRP antibodies would be implicated in complement-associated kidney vascular damage.

Right to left ventricular volume ratio is associated with mortality in congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is associated with high neonatal mortality. We performed this study to test the hypothesis that left ventricular (LV) and right ventricular (RV) volumes assessed by three-dimensional echocardiography may be associated with mortality in CDH. METHODS: This study was a single-center retrospective cohort study involving 35 infants with CDH. RV and LV end-diastolic volume (RVEDV and LVEDV, respectively) were measured by three-dimensional echocardiography and were corrected by birth body weight (BBW) on day 1. RVEDV/BBW, LVEDV/BBW, and LVEDV/RVEDV were compared between CDH survivors and non-survivors. Receiver-operating characteristic curve analysis was performed to assess the predictive ability for mortality of the echocardiographic parameters. RESULTS: Comparing CDH non-survivors (n = 6) with survivors (n = 29), respectively, RVEDV/BBW was significantly larger (2.54 ± 0.33 vs 1.86 ± 0.35 ml/kg; P < 0.01), LVEDV/BBW was significantly smaller (0.86 ± 0.21 vs 1.22 ± 0.33 ml/kg; P < 0.001), and LVEDV/RVEDV was significantly lower (0.34 ± 0.06 vs 0.66 ± 0.18; P < 0.001). The area under the curve for LVEDV/RVEDV was the largest (0.98). CONCLUSIONS: Three-dimensional echocardiographic volume imbalance between the RV and LV was remarkable in CDH non-survivors. The LVEDV/RVEDV ratio may be associated with mortality in CDH. IMPACT: Mortality with congenital diaphragmatic hernia (CDH) is high, and evaluating left and right ventricular structures and functions may be helpful in assessing the prognosis. Three-dimensional (3D) echocardiography indicated that the left ventricular end-diastolic volume/right ventricular end-diastolic volume ratio within 24 h after birth was associated with mortality in CDH infants. The usefulness of this ratio should be validated in prospective multicenter studies involving larger numbers of patients.

Efficacy and Safety of Dietary Undenatured Type II Collagen on Joint and Motor Function in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.

Prevalence of osteoarthritis (OA) is increasing alarmingly worldwide. Slowing down the progression of OA and diverse locomotive organ disorders is gaining interest in improving the quality of life (QOL) and extending healthy life-span. In a pilot study, intake of a small amount of undenatured type II collagen exhibited suppression of damage to the articular cartilage via oral immune tolerance. It also demonstrated improvement of knee and joint flexibility and mobility with continued intake of undenatured type II collagen (NEXT-II®) derived from chicken sternum cartilage. This randomized, double-blind, placebo-controlled, parallel-group clinical investigation (RCT) evaluated the efficacy and safety of 12 weeks of regular intake of NEXT-II® on joint and motor function in healthy Japanese male and female participants (aged 20 to <75 years).Sixty-four participants were randomized to receive either NEXT-II® (undenatured type II collagen 3.2 mg/d) or placebo over a period of 12 consecutive weeks. Efficacy on joint and motor functions were evaluated measuring knee passive range of motion as the primary outcome; the Japan Knee Osteoarthritis Measure (JKOM), Visual Analog Scale (VAS) for knee discomfort, and motor functions (10-meter walking and stair-climbing test) as the secondary outcomes; and Japan Low back pain Evaluation Questionnaire (JLEQ) and VAS for lower back discomfort as the exploratory outcomes.Fifty-eight participants (placebo = 28; NEXT-II® group = 30) completed the study. In the assessment of knee passive range of motion, significant improvements in "flexion" and "flexible angle (range)" were observed in the NEXT-II® group at 4, 8, and 12 weeks of treatment. NEXT-II® induced significant improvements in JKOM, VAS for knee and lower back discomfort, 10-meter walking test, stair-climbing test, and JLEQ.Results demonstrate that undenatured type II collagen is safe and efficacious in improving knee flexibility and mobility, reducing knee and lower back pain, and enhancing motor function.

[A Case of Pathological Complete Response for MSI-High Locally Advanced Unresectable Transverse Colon Cancer Treated with Nivolumab plus Ipilimumab Combination Therapy].

74-year-old woman was diagnosed with locally advanced unresectable transverse colon cancer. She started CAPOX therapy as first-line therapy after ileostomy. After second course, MSI-high was detected, so nivolumab plus ipilimumab combination therapy was started as second-line therapy. After 4 courses of combination therapy, she was judged to be in partial response and surgery was performed. Histopathological diagnosis of the surgical specimen showed complete response, and she is still alive without recurrence 15 months after surgery.

Impact of early mobilization on the duration of delirium in elderly hospitalized patients: A retrospective cohort pilot study.

Development of delirium during hospitalization impairs the activities of daily living in elderly hospitalized patients. In clinical practice, early mobilization from bed is recommended to reduce delirium incidence and hospitalization stay. However, the effects of early mobilization on elderly inpatients with delirium have not been established yet. The aim of this study was to investigate the association between early mobilization and the duration of delirium in elderly inpatients with delirium. This retrospective cohort pilot study examined 45 participants (23 males, 22 females; mean age: 84.5 ±â€…6.6 years), who developed delirium during hospitalization. Of the participants, 28 were surgically treated and 17 were non-surgically treated. We classified early or delayed mobilization based on the median number of days until the start of mobilization and compared after propensity score matching to adjust for baseline characteristics. Additionally, we examined the correlation between the number of days until the start of mobilization and the duration of delirium. The duration of delirium was significantly shorter in the early mobilization group, particularly in terms of sitting on the bed and wheelchair use than that in the delayed mobilization group {median: 4.0 [interquartile range (IQR): 2.0-6.0] vs 8.0 [IQR: 7.0-14.5] days, P = .013; median: 3.0 [IQR: 2.0-5.5] vs 11.0 [IQR: 7.5-14.5] days, P = .004, respectively}. Moreover, the duration of delirium significantly positively moderate correlated with the time until the start of sitting on the bed and wheelchair use (Spearman r = 0.527; P = .012, Spearman r = 0.630; P = .002, respectively). The results of this study suggest that early mobilization from sitting on the bed or wheelchair use after hospitalization or surgery may shorten the duration of delirium. Because the sample size of this pilot study is small, careful interpretation is needed, and further research is warranted.

Describing and Quantifying Wrong-Patient Medication Errors Through a Study of Incident Reports.

Purpose: Our aim was to inform a new definition of wrong-patient errors, obtained through an analysis of incident reports related to medication errors. Methods: We investigated wrong-patient medication errors in incident reports voluntarily reported by medical staff using a web-based incident reporting system from 2015 to 2016 at a university hospital in Japan. Incident report content was separately evaluated by four evaluators using investigational methods for clinical incidents from the Clinical Risk Unit and the Association of Litigation and Risk Management. They investigated whether it was the patient or drug that was incorrectly chosen during wrong-patient errors in drug administration in incident reports and assessed contributory factors which affected the error occurrence. The evaluators integrated the results and interpreted them together. Results: Out of a total 4337 IRs, only 30 cases (2%) contained wrong-patient errors in medication administration. The cases where the intended drugs were administered to incorrect patients occurred less frequently than cases where the wrong drugs were administered to the intended patients through the investigation of wrong targets. After a discussion, the evaluators concluded that the patient - drug/CPOE screen mismatch, caused by choosing the wrong patient, drug, or CPOE screen (mix-ups), occurred in the wrong-patient medication errors. These errors were caused by three conditions: (1) where two patients/drugs were listed next to one another, (2) where two patients' last names/drugs' names were the same, and (3) where the patient/drug/CPOE screen in front of the staff involved was believed to be the correct one. Additionally, these errors also involved insufficient confirmation, which led to failure to detect and correct the mismatch occurrences. Conclusion: Based on our study, we propose a new definition of wrong-patient medication errors: they consisted of choosing a wrong target and insufficient confirmation. We will investigate other types of wrong-patient errors to apply this definition.

Serious hazards of transfusion: evaluating the dangers of a wrong patient autologous salvaged blood in cardiac surgery.

BACKGROUND: The past half century has seen the near eradication of transfusion-associated hazards. Intraoperative cell salvage while widely used still poses significant risks and hazards due to human error. We report on a case in which blood collected from a patient with lung cancer was mistakenly administered to a patient undergoing cardiac surgery who should have received his own collected blood. The initial investigation found that the cause of the patient harm was violations of procedures by hospital personnel. A detailed investigation revealed that not only violations were the cause, but also that the underlying causes included haphazard organizational policies, poor communication, workload and staffing deficiencies, human factors and cultural challenges. CASE PRESENTATION: On August 14, 2019, a 72-year-old male was admitted to our hospital for angina pectoris and multivessel coronary artery disease. Cardiac surgery was performed using an autologous salvage blood collection system, and there were no major problems other than the prolonged operation time. During the night after the surgery, when the patient's blood pressure dropped, a nurse retrieved a blood bag from the ICU refrigerator that had been collected during the surgery and administered it at the physician's direction, but at this time neither the physician nor the nurse performed the required checking procedures. The blood administered was another patient's blood taken from another surgery the day before; an ABO mismatch transfusion occurred and the patient was diagnosed with DIC. The patient was discharged 65 days later after numerous interventions to support the patient. An accident investigation committee was convened to analyze the root causes and develop countermeasures to prevent a recurrence. CONCLUSION: This adverse event occurred because the protocol for intraoperative blood salvage management was not clearly defined, and the procedure was different from the standard transfusion practices. We developed a new workflow based on a human factors grounded, systems-wide improvement strategy in which intraoperative blood collection would be administered before the patient leaves the operating room to completely prevent recurrence, instead of simply requiring front-line staff to do a double-check. Implementing strong systems processes can reduce the risk of errors, improve the reliability of the work processes and reduce the likelihood of patient harm occurring in the future.

Effect of Dietary Pyrroloquinoline Quinone Disodium Salt on Cognitive Function in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.

BACKGROUND: Cognitive dysfunctions are increasing alarmingly around the world, and researchers are exploring preventive measures for improving brain performance. Pyrroloquinoline quinone (PQQ), a naturally occurring coenzyme in foods, exhibits potent antioxidant activity, and improves diverse functions which include mitochondrial activation, growth, repair, protection of nerve cells by increased expression of nerve growth factor (NGF) and NGF receptors; and suppression of fibril formation and aggregation of amyloid ß. OBJECTIVE: This randomized, double-blind, placebo-controlled, parallel-group clinical investigation (RCT) evaluated the efficacy and safety of PQQ disodium salt powder (mnemoPQQ®) for improved cognitive function after 12 weeks of supplementation in healthy Japanese male and female (age 40 to <80 Y). METHODS: 64 healthy subjects were randomly assigned to receive either mnemoPQQ® (PQQ disodium salt: 21.5 mg/day) or a placebo over a period of 12 weeks. The efficacy of mnemoPQQ® on cognitive performance (memory, attention, judgment, and cognitive flexibility) was examined using Cognitrax as the primary outcome (primary endpoint), and forgetfulness questionnaire (DECO: Deterioration Cognitive Observee) and Mini-Mental State Examination-Japanese (MMSE-J) as the secondary outcome (secondary endpoint). RESULTS: A total of 58 subjects (placebo = 31; Age = 70.91 ± 3.06 Y; mnemoPQQ® group = 27; Age = 72.10 ± 3.77 Y) completed the study over a period of 12 weeks of supplementation. Significant improvements were observed on the Cognitrax's cognitive function domain score on "composite memory", "verbal memory", "reaction time", "complex attention", "cognitive flexibility", "executive function", and "motor speed" in the mnemoPQQ® group as compared to the placebo group. The DECO and the MMSE-J scores were also significantly improved in the mnemoPQQ® group. No adverse events were observed. CONCLUSIONS: Study demonstrates that supplementation of PQQ disodium salt is useful in improving memory, attention, judgment, and cognitive function, in middle-aged to elderly population, who feel they have become more forgetful because of aging.

R3hdml regulates satellite cell proliferation and differentiation.

In this study, we identified a previously uncharacterized skeletal satellite cell-secreted protein, R3h domain containing-like (R3hdml). Expression of R3hdml increases during skeletal muscle development and differentiation in mice. Body weight and skeletal muscle mass of R3hdml knockout (KO) mice are lower compared to control mice. Expression levels of cell cycle-related markers, phosphorylation of Akt, and expression of insulin-like growth factor within the skeletal muscle are reduced in R3hdml KO mice compared to control mice. Expression of R3hdml increases during muscle regeneration in response to cardiotoxin (CTX)-induced muscle injury. Recovery of handgrip strength after CTX injection was significantly impaired in R3hdml KO mice, which is rescued by R3hdml. Our results indicate that R3hdml is required for skeletal muscle development, regeneration, and, in particular, satellite cell proliferation and differentiation.

Green light-emitting diode phototherapy for neonatal hyperbilirubinemia: Randomized controlled trial.

BACKGROUND: The main photochemical pathway in phototherapy for neonatal hyperbilirubinemia is the production and elimination (in bile or urine) of cyclobilirubin, which is a structural photoisomer of bilirubin, and which is most efficiently produced by green light. Green light-emitting diode (LED) phototherapy, however, has not been evaluated in the clinical setting because it is not recommended in American Academy of Pediatrics guidelines. We therefore compared the efficacy of green LED phototherapy and blue LED phototherapy in patients with neonatal hyperbilirubinemia. METHODS: In this prospective randomized controlled trial, neonates with hyperbilirubinemia were randomly allocated to a green LED or blue LED phototherapy group. Both groups underwent 24 h of phototherapy, and blood was sampled before and after 24 h of phototherapy. Total serum bilirubin (TSB) was measured using enzymatic methods and bilirubin photoisomers were measured on high-performance liquid chromatography. RESULTS: Thirty-four infants were randomized (green, n = 16; blue, n = 18). TSB decreased significantly from 15.3 ± 1.5 to 13.9 ± 1.5 mg/dL in the green LED group (P < 0.01) and from 16.2 ± 1.3 to 14.5 ± 1.7 mg/dL in the blue LED group (P < 0.01) after 24 h of phototherapy. No significant difference was found in TSB reduction after phototherapy between the groups. CONCLUSIONS: Both light sources produced a significant reduction in TSB, indicating clinical effectiveness.

Optical silencing of body wall muscles induces pumping inhibition in Caenorhabditis elegans.

Feeding, a vital behavior in animals, is modulated depending on internal and external factors. In the nematode Caenorhabditis elegans, the feeding organ called the pharynx ingests food by pumping driven by the pharyngeal muscles. Here we report that optical silencing of the body wall muscles, which drive the locomotory movement of worms, affects pumping. In worms expressing the Arch proton pump or the ACR2 anion channel in the body wall muscle cells, the pumping rate decreases after activation of Arch or ACR2 with light illumination, and recovers gradually after terminating illumination. Pumping was similarly inhibited by illumination in locomotion-defective mutants carrying Arch, suggesting that perturbation of locomotory movement is not critical for pumping inhibition. Analysis of mutants and cell ablation experiments showed that the signals mediating the pumping inhibition response triggered by activation of Arch with weak light are transferred mainly through two pathways: one involving gap junction-dependent mechanisms through pharyngeal I1 neurons, which mediate fast signals, and the other involving dense-core vesicle-dependent mechanisms, which mediate slow signals. Activation of Arch with strong light inhibited pumping strongly in a manner that does not rely on either gap junction-dependent or dense-core vesicle-dependent mechanisms. Our study revealed a new aspect of the neural and neuroendocrine controls of pumping initiated from the body wall muscles.

Detection Method for Aquatic Bacteria of the Fingers, as a Potential Origin of the Aqueous Solution Contamination.

　Aquatic bacteria were isolated from the hands of working staffs by an adapted culture protocol. When the sample solution obtained by the" glove juice method" was incubated for 3 days at room temperature, viable cell counts increased up to 105-fold, and the majority of the isolated colonies were shown to be Gram-negative aquatic bacteria, which carry the risk of contaminating water. Using R2A medium, coagulase-negative staphylococci were the dominant microbes immediately after recovery from the hands. Here it was revealed that bacteria of the phylum Proteobacteria isolated from the hand can be the causative bacteria of aqueous contamination. This modification in the GJ method may be useful as an effective training protocol to demonstrate the importance of hand hygiene and clean operation for aseptic manufacturing.

Short-term desensitization of fast escape behavior associated with suppression of Mauthner cell activity in larval zebrafish.

Escape is among the simplest animal behaviors employed to study the neural mechanisms underlying learning. Teleost fishes exhibit behavioral learning of fast escape initiated with a C-shaped body bend (C-start). C-starts are subdivided into short-latency (SLC) and long-latency (LLC) types in larval zebrafish. Whether these two can be separately modified, and the neural correlates of this modification, however, remains undetermined. We thus performed Ca2+ imaging of Mauthner (M-) cells, a pair of giant hindbrain neurons constituting a core element of SLC circuit, during behavioral learning in larval zebrafish. The Ca2+ response corresponding to a single spiking of the M-cells was coupled with SLCs but not LLCs. Conditioning with a repeated weak sound at subthreshold intensity to elicit C-starts selectively suppressed SLC occurrence for 10min without affecting LLC responsiveness. The short-term desensitization of SLC was associated with the suppression of M-cell activity, suggesting that changes in single neuron responsiveness mediate behavioral learning. The conditioning did not affect the acoustically evoked mechanotransduction of inner ear hair cells, further suggesting plastic change in transmission efficacy within the auditory input circuit between the hair cells and the M-cell.

Changes in job stress and coping skills among caregivers after dementia care practitioner training.

BACKGROUND: Dementia care practitioner training is essential for professional caregivers to acquire medical knowledge and care skills for dementia patients. We investigated the significance of training in stress management by evaluating caregivers' job stress and coping style before and after they have completed training. METHODS: The subjects included 134 professional caregivers (41 men, 93 women) recruited from participants in training programmes held in Kanagawa Prefecture from August 2008 to March 2010. A survey using a brief job stress questionnaire and a coping scale was carried out before and after they completed their training. A t-test and multiple regression analysis were performed to evaluate the effects of the training. RESULT: After the training, the scores of modifiers on the job stress scale and of the coping scale increased, whereas the scores of stress reactions on the job stress scale decreased. However, there were no changes in participants' subjective cognition concerning their workplace environment. Furthermore, the change in stress reaction score tended to correlate with the change in consultation score in all participants and with the change in problem-solving and consultation in male participants. Among female participants, the change in stress reaction score tended to correlate with change in support from superiors and colleagues as modifiers. The factors that correlated to the change in stress reaction score differed between genders. CONCLUSION: The findings suggest that training caregivers improves their stress reaction and coping skills.

X-ray Crystallographic Structure of Thermophilic Rhodopsin: IMPLICATIONS FOR HIGH THERMAL STABILITY AND OPTOGENETIC FUNCTION.

Thermophilic rhodopsin (TR) is a photoreceptor protein with an extremely high thermal stability and the first characterized light-driven electrogenic proton pump derived from the extreme thermophile Thermus thermophilus JL-18. In this study, we confirmed its high thermal stability compared with other microbial rhodopsins and also report the potential availability of TR for optogenetics as a light-induced neural silencer. The x-ray crystal structure of TR revealed that its overall structure is quite similar to that of xanthorhodopsin, including the presence of a putative binding site for a carotenoid antenna; but several distinct structural characteristics of TR, including a decreased surface charge and a larger number of hydrophobic residues and aromatic-aromatic interactions, were also clarified. Based on the crystal structure, the structural changes of TR upon thermal stimulation were investigated by molecular dynamics simulations. The simulations revealed the presence of a thermally induced structural substate in which an increase of hydrophobic interactions in the extracellular domain, the movement of extracellular domains, the formation of a hydrogen bond, and the tilting of transmembrane helices were observed. From the computational and mutational analysis, we propose that an extracellular LPGG motif between helices F and G plays an important role in the thermal stability, acting as a "thermal sensor." These findings will be valuable for understanding retinal proteins with regard to high protein stability and high optogenetic performance.

Broadband coherent Raman spectroscopy running at 24,000 spectra per second.

We present a Fourier-transform coherent anti-Stokes Raman scattering (FT-CARS) spectroscopy technique that achieves broadband CARS measurements at an ultrahigh scan rate of more than 20,000 spectra/s - more than 20 times higher than that of previous broadband coherent Raman scattering spectroscopy techniques. This is made possible by an integration of a FT-CARS system and a rapid-scanning retro-reflective optical path length scanner. To demonstrate the technique's strength, we use it to perform broadband CARS spectroscopy of the transient mixing dynamics of toluene and benzene in the fingerprint region (200-1500 cm(-1)) with spectral resolution of 10 cm(-1) at a record high scan rate of 24,000 spectra/s. Our rapid-scanning FT-CARS technique holds great promise for studying chemical dynamics and wide-field label-free biomedical imaging.

Effects of extracellular pH and hypoxia on the function and development of antigen-specific cytotoxic T lymphocytes.

The major effector cells for cellular adaptive immunity are CD8(+) cytotoxic T lymphocytes (CTLs), which can recognize and kill virus-infected cells and tumor cells. Although CTLs exhibit strong cytolytic activity against target cells in vitro, a number of studies have demonstrated that their function is often impaired within tumors. Nevertheless, CTLs can regain their cytotoxic ability after escaping from the tumor environment, suggesting that the milieu created by tumors may affect the function of CTLs. As for the tumor environment, the patho-physiological situation present in vivo has been shown to differ from in vitro experimental conditions. In particular, low pH and hypoxia are the most important microenvironmental factors within growing tumors. In the present study, to determine the effect of these factors on CTL function in vivo, we examined the cytolytic activity of CTLs against their targets using murine CTL lines and the induction of these cells from memory cells under low pH or hypoxic conditions using antigen-primed spleen cells. The results indicated that both cytotoxic activity and the induction of functional CTLs were markedly inhibited under low pH. In contrast, in hypoxic conditions, although cytotoxic activity was almost unchanged, the induction of CTLs in vitro showed a slight enhancement, which was completely abrogated in low pH conditions. Therefore, antigen-specific CTL functions may be more vulnerable to low pH than to the oxygen concentration in vivo. The findings shown here provide new therapeutic approaches for controlling tumor growth by retaining CTL cytotoxicity through the maintenance of higher pH conditions.

[Nonconvulsive status epilepticus in neurological emergencies].

According to the 2010 neuroresuscitation guideline, status epilepticus (SE) is a critical condition that causes respiratory and circulation dysfunction, including "acute consciousness disturbance" and "elevated intracranial pressure." There are two types of SE: general convulsive SE (GCSE) and nonconvulsive SE (NCSE). GCSE is easily diagnosed because the patients show continuous convulsions. In contrast, NCSE can only be diagnosed by electroencephalography (EEG), which can delay diagnosis. Moreover, GCSE and NCSE occasionally manifest in the same patient and alternate. Here, we describe the case of a 64-year-old male patient who experienced losses of consciousness mimicking stroke. We could not diagnose these episodes as NCSE until the patient had a general continuous convulsion. In this case, the delayed diagnosis of NCSE resulted in uncontrollable GCSE that required intensive management, including mechanical ventilation under sedation. It is important to recognize that NCSE can cause consciousness disturbance and to initiate treatment as soon as possible to improve patient prognosis. This could be achieved by performing an EEG earlier, such as at the scene of emergencies.