Ordinal Time Series Forecasting of the Air Quality Index.

This research models and forecasts daily AQI (air quality index) levels in 16 cities/counties of Taiwan, examines their AQI level forecast performance via a rolling window approach over a one-year validation period, including multi-level forecast classification, and measures the forecast accuracy rates. We employ statistical modeling and machine learning with three weather covariates of daily accumulated precipitation, temperature, and wind direction and also include seasonal dummy variables. The study utilizes four models to forecast air quality levels: (1) an autoregressive model with exogenous variables and GARCH (generalized autoregressive conditional heteroskedasticity) errors; (2) an autoregressive multinomial logistic regression; (3) multi-class classification by support vector machine (SVM); (4) neural network autoregression with exogenous variable (NNARX). These models relate to lag-1 AQI values and the previous day's weather covariates (precipitation and temperature), while wind direction serves as an hour-lag effect based on the idea of nowcasting. The results demonstrate that autoregressive multinomial logistic regression and the SVM method are the best choices for AQI-level predictions regarding the high average and low variation accuracy rates.

Vinpocetine inhibits glutamate release induced by the convulsive agent 4-aminopyridine more potently than several antiepileptic drugs.

4-Aminopyridine (4-AP) is a convulsing agent that in vivo preferentially releases Glu, the most important excitatory amino acid neurotransmitter in the brain. Here the ionic dependence of 4-AP-induced Glu release and the effects of several of the most common antiepileptic drugs (AEDs) and of the new potential AED, vinpocetine on 4-AP-induced Glu release were characterized in hippocampus isolated nerve endings pre-loaded with labelled Glu ([3H]Glu). 4-AP-induced [3H]Glu release was composed by a tetrodotoxin (TTX) sensitive and external Ca2+ dependent fraction and a TTX insensitive fraction that was sensitive to the excitatory amino acid transporter inhibitor, TBOA. The AEDs: carbamazepine, phenytoin, lamotrigine and oxcarbazepine at the highest dose tested only reduced [3H]Glu release to 4-AP between 50-60%, and topiramate was ineffective. Vinpocetine at a much lower concentration than the above AEDs, abolished [3H]Glu release to 4-AP. We conclude that the decrease in [3H]Glu release linked to the direct blockade of presynaptic Na+ channels, may importantly contribute to the anticonvulsant actions of all the drugs tested here (except topiramate); and that the significantly greater vinpocetine effect in magnitude and potency on [3H]Glu release when excitability is exacerbated like during seizures, may involve the increase additionally exerted by vinpocetine in some K+ channels permeability.

Pharmacokinetics of intravenous azithromycin and ceftriaxone when administered alone and concurrently to healthy volunteers.

This study was conducted to identify whether or not a pharmacokinetic interaction existed when azithromycin and ceftriaxone were administered concurrently. This randomized, open-label, three-way crossover study in 12 healthy volunteers characterized the plasma pharmacokinetic parameter profiles of both drugs, as well as the white blood cell uptake and exposure to azithromycin, when the drugs were administered alone and together. The plasma pharmacokinetic parameters for azithromycin and ceftriaxone did not differ significantly either after a single dose or at steady state when the two were co-administered as opposed to being administered alone. Moreover, the neutrophil and monocyte/lymphocyte peak azithromycin concentrations and sampling period exposures also did not differ significantly between the study arm and the control arm. This study confirms that there is no interaction between azithromycin and ceftriaxone when they are administered concurrently.

Both TPA and SCC-Ag levels are prognostic even in high-risk stage Ib-IIa cervical carcinoma as determined by a stratification analysis.

OBJECTIVE: To determine the prognostic values of tissue polypeptide antigen (TPA), squamous cell carcinoma antigen (SCC-Ag), and carcinoembryonic antigen (CEA) in the sera of cervical carcinoma patients, especially in those with a poor prognosis. METHODS: In this retrospective study, the preoperative serum SCC-Ag, TPA, and CEA were analyzed in 779 patients with cervical squamous cell carcinoma of stage Ib-IIa who received radical hysterectomy and pelvic lymph node dissection (RAH-PLND) between 1984 and 1994. RESULTS: Due to poor predictive value and poor correlation between serum CEA and clinico-pathological factors, CEA was abandoned in this study. Elevated TPA and SCC-Ag levels, pelvic lymph node metastasis (PLNM), lymphvascular space involvement (LVSI) and deep stromal invasion (DSI) were associated with poor survival time by univariate analysis. The correlation study showed that elevated serum TPA was significantly related to PLNM, LVSI, and DSI (p = 0.004, 0.008, and 0.021, respectively), and SCC-Ag was related to PLNM and bulky tumor size (p = 0.001 and 0.02, respectively). In the multivariate analysis, only PLNM and LVSI remained independently significant indicating poor survival. Further stratification studies by PLNM and LVSI showed that elevated TPA levels could even indicate higher recurrence rates in patients with PLNM (p = 0.045), as well as SCC-Ag in patients with LVSI (p = 0.038). CONCLUSIONS: The results suggest that both elevated TPA and SCC-Ag levels depicting poor prognosis in stage Ib-IIa cervical SCC, especially indicates a group of high-risk patients who may need more aggressive therapy.

The Kinmen women-health investigation (KIWI): a menopausal study of a population aged 40-54.

OBJECTIVES: This paper aims to report the methodology of a study of a cohort of middle-aged women in Taiwan, their age at menopause, and related factors and prevalence of menopausal symptoms, and to examine the relationships between symptoms and sociodemographic variables. METHODS: An epidemiological study of neuropsychological change during the menopausal transition among Chinese women aged 40-54 years old on the islet of Kinmen. RESULTS: Of a targeted population of 2256 individuals, 1497 (66%) participated in the study. The mean age at menarche was 15.6 years and that at menopause was 48 years. The hormone use rate at the time of study was 23% in surgical menopausal women, and 9% were past users. After excluding surgical menopausal and premenopausal women, 6% reported a current use of estrogen replacement therapy and 6% were past users. The most frequently reported discomforts for those women aged >45 were troubled sleep, backaches, and joint pain. Four symptom clusters: musculoskeletal, non-specific somatic complaints, urogenital, and vasomotor, were identified. After adjustment for age, the urogenital and vasomotor symptoms were significantly associated with menopausal status. CONCLUSIONS: The age at menopause did not differ much from Western studies, but the menopausal symptoms, especially the vasomotor symptoms, were much lower in our study population. Nevertheless, vasomotor symptoms were still significantly associated with menopausal status.

Review of pre-eclampsia in Taiwan: a multi-institutional study.

BACKGROUND: Because the reported frequency of pre-eclampsia in Taiwan varies significantly, the aims of this study were to measure the current incidence of pre-eclampsia and its correlated morbidity and mortality for both mothers and fetuses in Taiwan. METHODS: We retrospectively studied all reported cases of pre-eclampsia and eclampsia from January 1, 1993 to December 31, 1997 in the 14 tertiary medical centers and regional hospitals in Taiwan. Recruiting criteria were pregnancy-induced hypertension (systolic blood pressure > or = 140 mmHg or diastolic blood pressure > or = 90 mmHg) with proteinuria (> or = 300 mg of urinary protein per 24 hours) and independent part edema. RESULTS: There were 4,193 patients with pre-eclampsia and eclampsia for a frequency of 2.03% of 206,551 deliveries during the study period. Of these, 58.9% of patients were classified as having mild pre-eclampsia while 38.4% had severe pre-eclampsia. Advanced maternal age (> 35 years) (odds ratio [OR] = 4.56; 95% confidence interval [CI] = 4.23-4.90; p < 0.001), primiparity (OR = 1.71; 95% CI = 1.61-1.82; p = 0.02) and twin pregnancy (OR = 1.92; 95% CI = 1.64-2.25; p = 0.01) were significant risk factors for developing pre-eclampsia. However, multivariate analysis showed that only advanced maternal age was a significant risk factor for pre-eclampsia (OR = 3.21; 95% CI = 2.95-3.50; p < 0.001). In contrast to mild pre-eclampsia, severe pre-eclampsia resulted in significantly worse outcomes for both mothers and fetuses. Complications in patients with severe pre-eclampsia included placental abruption, acute renal failure, pulmonary edema, postpartum hemorrhage, pleural effusion, preterm labor, intrauterine growth retardation, stillbirth, neonatal mortality and low birth weight infants, all of which occurred significantly more frequently than in patients with mild pre-eclampsia (p < 0.001). CONCLUSIONS: Pre-eclampsia remains a big challenge in modern obstetrics in Taiwan. Early diagnosis and management of patients with pre-eclampsia to prevent progression would significantly improve outcomes for mothers and fetuses.

Borderline ovarian tumors complicating pregnancy: a case report.

Although the majority of ovarian tumors complicating pregnancy are benign, they still pose a challenge because of the difficulty in differentiating between benign and malignant tumors during pregnancy. To our knowledge, the value of color Doppler ultrasound in the diagnosis of borderline malignant tumors complicating pregnancy remains unclear. We present the case of a 29-year-old pregnant woman with an ovarian tumor of low malignant potential. Preoperative ultrasound revealed a well-encapsulated cystic complex on the left ovary measuring 16 x 18 x 12 cm with an internally smooth surface, multiple septa ranging from 2 to 4 mm in thickness and a small solid component 2 cm in diameter, with a resistance index of 0.42. The differential diagnosis preoperatively was a borderline tumor. The patient underwent a left oophorectomy at 18 weeks of gestation. Frozen pathology indicated a mucinous cystadenocarcinoma of low malignant potential. A thorough surgical staging was completed. The final pathology confirmed mucinous cystadenocarcinoma of low malignant potential, stage IA. Postoperatively, the patient had an uneventful course and did not receive any adjuvant therapy. She delivered a normal male fetus weighing 3,450 g at 38 weeks of gestation. We conclude that color Doppler ultrasound is helpful for the preoperative diagnosis of borderline tumors of the ovaries but its usefulness for making an accurate diagnosis may require further evaluation.

Study on the possible involvement of protein kinases in the modulation of brain presynaptic sodium channels; comparison with calcium channels.

A possible modulatory role of kinases on voltage sensitive Na+ channels of presynaptic brain nerve endings was investigated by testing the effect of several kinase activators and inhibitors on the elevation of [Nai] induced by veratridine in mouse brain synaptosomes loaded with a selective Na+ indicator dye. Veratridine (20 microM) increases the basal [Nai] level (20 mM) more than twofold. This increase is independent of external Ca2+, but abolished by tetrodotoxin (1 microM). Activation of cAMP dependent protein kinase with forskolin or cAMP analogs, or of protein kinase C with diacylglycerol did not affect the veratridine-induced elevation in [Nai]. Drugs reported to inhibit calmodulin-dependent events, as well as the regulatory domain of protein kinase C, were potent and effective inhibitors of the increase in [Nai] induced by veratridine, as well as other veratridine induced responses, namely elevation of [Cai] (monitored with the Ca2+ indicator dye fura-2) and neurotransmitter (GABA) release. Drugs that inhibit kinases by binding to the catalytic site were ineffective, however, as was the phosphatase inhibitor, okadaic acid. A selective inhibitor of Ca2+ and calmodulin dependent protein kinase II also did not affect the elevation of [Nai] induced by veratridine, but markedly diminished the elevation of [Cai] induced by depolarization either with veratridine or with high K+ (15 and 30 mM). On the basis of these results it is concluded that, the dramatic inhibition exerted by some of the drugs tested on the elevation of [Nai] induced by veratridine is not due to their effects on kinases, but to a possible interaction of these compounds with an intracellular site of the Na+ channel. On the other hand, while Ca2+ and calmodulin dependent protein kinase II is unable to modulate brain presynaptic voltage sensitive Na+ channels, it facilitates the activation of brain presynaptic voltage sensitive Ca2+ channels.

Fever of unknown origin in the puerperium. A case report.

BACKGROUND: Postpartum fever is a common problem for obstetricians, but fever of unknown origin (FUO) occurring in the puerperium may be relatively unfamiliar and a challenge to the majority of obstetricians. CASE: A 29-year-old woman had a FUO detected during the puerperium. Despite serial examinations and therapeutic trials, the fever persisted for three weeks without a clinical improvement or definite infection source. The presence of a huge uterine myoma was observed. The patient finally underwent myomectomy, and a pathology review revealed a cellular leiomyoma associated with massive infarction and acute inflammation. The fever subsided substantially on the third day postoperatively. CONCLUSION: Although a uterine leiomyoma as a cause of fever in the puerperium is not new, rarely does it cause prolonged fever. It should be taken into consideration in pregnant women known to have uterine myomas during pregnancy and in the puerperium, especially if FUO develops. Nonsteroidal antiinflammatory drugs can be a tool for making the differential diagnosis in such a patient, and exploratory laparotomy can be delayed until an emergency condition occurred, especially important during pregnancy.

omega-Aga IVA selectively inhibits the calcium-dependent fraction of the evoked release of [3H]GABA from synaptosomes.

The effect of omega-Aga IVA, a P-type Ca2+ channel blocker, on the release of the inhibitory neurotransmitter GABA and on the elevation of Cai induced by depolarization was investigated in [3H]GABA and fura-2 preloaded mouse brain synaptosomes, respectively. Two strategies (i.e. 20 mM external K+ and veratridine) that depolarize by different mechanisms the preparation were used. High K+ elevates Cai and induces [3H]GABA release in the absence of external Na+ and in the presence of TTX, conditions that abolish veratridine induced responses. The effect of omega-Aga IVA on the Ca2+ and Na+ dependent fractions of the depolarization evoked release of [3H]GABA were separately investigated in synaptosomes depolarized with high K+ in the absence of external Na+ and with veratridine in the absence of external Ca2+, respectively. The Ca2+ dependent fraction of the evoked release of [3H]GABA and the elevation of Ca2+ induced by high K+ are markedly inhibited (about 50%) in synaptosomes exposed to omega-Aga IVA (300 nM) for 3 min before depolarization, whereas the Na+ dependent, Ca2+ independent carrier mediated release of [3H]GABA induced by veratridine, which is sensitive to verapamil and amiloride, is not modified by omega-Aga IVA. Our results indicate that an omega-Aga IVA sensitive type of Ca2+ channel is highly involved in GABA exocytosis.

Characterization of the type of calcium channel primarily regulating GABA exocytosis from brain nerve endings.

In an attempt to further characterize the type of Ca2+ channels primarily regulating GABA exocytosis, the effects of increasing concentrations of omega CTx MVIIC,-omega-Aga IVA and other Ca2+ channel blockers (nitrendipine, Cd2+ and Ni2+), commonly used for pharmacologically discerning among the various types of Ca2+ channels, were tested on the dissected Ca2+ dependent fraction of the depolarization evoked release of GABA from mouse brain synaptosomes. Our results show that omega-CTx MVIIC inhibits GABA exocytosis with a calculated IC50 of 3 microM and omega-Aga IVA with a calculated IC50 of 50 nM. The divalent cation Cd2+ only diminishes GABA exocytosis at 70 microM, but does not modify this response at lower concentrations (i.e. 1 and 10 microM). Neither nitrendipine (10 microM) nor Ni2+ (100 microM and 500 microM) modified GABA exocytosis. The failure of nitrendipine at a high concentration to inhibit GABA exocytosis discards L-type Ca2+ channels as the main regulators of this response; likewise that of Ni2+ discards Ca2+ channels of the N-type, and the failure of nM concentrations of omega-CTx MVIIC or 500 microM Ni2+, also discards alpha 1A/Q-type Ca2+ channels as the main regulators of the GABA response. On the basis of these results and in particular of the higher potency of omega-Aga IVA than omega-CTx MVIIC, it is concluded that the type of Ca2+ channels that primarily determine the exocytosis of GABA belong to a P-like type of Ca2+ channels.

A role for calcium/calmodulin kinase(s) in the regulation of GABA exocytosis.

A possible role for protein kinases in the regulation of GABA exocytosis in nerve endings was investigated. The effect on the release of the radioactive neurotransmitter ([3H]GABA) from mouse brain synaptosomes of several protein kinase inhibitors was estimated after treatment with 37 mM K+ in the absence of external Na+, a condition under which [3H]GABA release is completely Ca2+ dependent. Among the inhibitors one group inhibit the kinases by the catalytic site (i.e. staurosporine and H7) and others (TFP, sphingosine and W7) act on the regulatory site of protein kinases. The compounds of the second group, which are reported to inhibit calmodulin dependent events and the increase in cytosolic Ca2+ (Cai) induced by high K+ depolarization, were the most efficient inhibitors of [3H]GABA release. The selective inhibitor of CaMPK II, KN-62, also markedly diminished [3]GABA release as well as the increase in Cai induced by high K+. The kinase inhibitors from the first group that are unable to diminish the increase in Cai induced by high K+ were also less efficient inhibitors of [3H]GABA release even at high concentrations. The present results indicate that at the doses tested all the drugs inhibit to some extent the release of the Ca2+ dependent fraction of [3H]GABA perhaps by inhibiting a CaMPK II mediated phosphorylation step triggered by depolarization and facilitated by the elevation of Cai. In addition, the second group of antagonists and KN-62 inhibit the elevation of Cai to high K+ thus exhibiting a higher efficiency on [3H]GABA release than the first group of antagonists.

Dopamine transporter mediated release of dopamine: role of chloride.

Using a rapid (0.5 ml/min) flow rate superfusion system, the dopamine (DA) transporter mediated release of DA is further explored, and compared to the depolarization evoked release of DA in rat striatal synaptosomes preloaded with radioactive DA (3H-DA). In this system external DA in the low microM range efficaciously releases the preloaded transmitter, the maximal response being reached at 3 microM DA. The external DA stimulated release is Ca(2+)-independent, Cl(-)-dependent, and blocked by both bupropion and nomifensine. The atypical antidepressant bupropion inhibits 3H-DA accumulation to rat striatal synaptosomes with a calculated IC50 of 1.3 x 10(-6) M. Among DA uptake blockers some are known to act as DA releasing agents. Here we found that the DA uptake blocker nomifensine (30 microM) is unable to modify the baseline release of 3H-DA, whereas bupropion (10 microM) clearly elevates the baseline release of 3H-DA in a Ca(2+)-independent and Cl(-)-dependent manner. The non releasing agent nomifensine blocks the release of 3H-DA induced by bupropion. The Ca(2+)-dependent, high K+ depolarization evoked release of 3H-DA is not modified by nomifensine and does not depend on the external Cl- concentration. When the depolarizing medium contains DA the carrier mediated release of 3H-DA induced by the external DA is additive to the high K+ induced response. A drastic drop in the external Cl- concentration induces 3H-DA release. This release of 3H-DA induced by low external Cl- levels is completely blocked by nomifensine, which only slightly diminished the release of 3H-DA induced by the absence of external Na+. On the basis of these results, it is concluded that: 1) Rapid perfusion flow rates eliminate DA reuptake. 2) DA uptake inhibitors either with or without DA releasing capabilities block the release of DA induced by microM levels of external DA. 3) By preventing translocation of the DA transporter mobile moiety, nomifensine may inhibit the release of DA induced by external DA or bupropion and by drastic drops in the external Cl- concentration. 4) In the absence of nomifensine, the DA transporter works under both resting and depolarized conditions, but in contrast to the GABA transporter (Sitges et al.: Neurochem Res 18:1081-1087, 1993), the DA transporter does not contribute to the amount of the DA released by depolarization. 5) Reversal of the DA uptake carrier is favored by conditions increasing the internal DA levels. 6) Cl- rather than Na+ is a major determinant in 3H-DA movements through the DA transporter.

Vesicular and carrier-mediated depolarization-induced release of [3H]GABA: inhibition by amiloride and verapamil.

The Ca(2+)-dependent, presumably exocytotic fraction of the [3H]GABA released by depolarization is dissected from the depolarization-induced Na(+)-dependent, carrier-mediated fraction of [3H]GABA release in mouse brain synaptosomes. GABA homoexchange is prevented by the [3H]GABA carrier blocker, DABA. The absence of external Na+ completely abolishes the release of the carrier-mediated, presumably cytoplasmic release of [3H]GABA induced by homoexchange and heteroexchange with GABA and DABA, respectively. The carrier-mediated, Na(+)-dependent fraction of the depolarization-induced release of [3H]GABA is resistant to tetrodotoxin (TTX) but is sensitive to amiloride and verapamil. The Ca(2+)-dependent fraction of the [3H]GABA released by high K+ depolarization is also completely abolished by amiloride (from 300 microM) and sensitive to verapamil (30 microM), but in contrast is insensitive to the absence of external Na+ and to DABA. On the basis of these results we conclude that amiloride and verapamil inhibit high K(+)-induced release of [3H]GABA by antagonizing the entrance of Ca2+ (and possibly Na+ when external Ca2+ is absent) through a population of voltage sensitive presynaptic Ca2+ channels activated by depolarization.

The effect of verapamil on GABA and dopamine release does not involve voltage-sensitive calcium channels.

The effect of verapamil, which belongs to the group of drugs collectively referred to as 'organic Ca2+ channel blockers', was investigated on the basal and stimulated release of the neurotransmitters dopamine and GABA in rat striatum synaptosomes. Verapamil inhibits the Na(+)-dependent release of GABA in response to depolarization with an IC50 of 25 microM, whereas it is unable to modify the Na2(+)-independent, Ca2(+)-dependent fraction of GABA release induced by high K+ depolarization. Verapamil does not modify the basal release of GABA but stimulates the basal release of dopamine in a dose-dependent manner (ED50 5 microM). This verapamil-induced outflow of dopamine is independent of Ca2+ and occurs in the presence of tetrodotoxin, indicating that it is not mediated by voltage-sensitive Ca2+ or Na+ channels of the presynaptic membrane. Dopamine release induced by verapamil is cumulative with that induced by depolarizing agents (high K+ or veratridine). As verapamil, pimozide, a neuroleptic of the diphenylbutylpiperidine type, increases the basal and stimulated release of dopamine. We conclude that the opposite effects of verapamil of GABA and dopamine release are due to differences in the releasable fractions of these 2 types of neurotransmitters. Besides, none of these effects are directly linked with the blockade of voltage-operated Ca2+ channels of the presynaptic membrane.