Genome mining of a NRPS-like gene cluster led to the identification of two novel alkaloids with antimicrobial activity. This work reveals the huge potential of NRPS-like biosynthetic gene clusters in the discovery of novel natural products.

rapidly modulates mustard oil-induced visceral hypersensitivity in conscious female rats: a role of CREB phosphorylation in spinal dorsal horn neurons. Am J Physiol Gastrointest Liver Physiol 292: G438 -G446, 2007. First published September 14, 2006; doi:10.1152/ajpgi.00210.2006.-This study investigated the effect of sex hormones on mustard oil (MO)-induced visceral hypersensitivity in female rats and analyzed possible involved signaling pathways. Female rats, either intact or ovariectomized (OVX), were prepared for abdominal muscle electromyography in response to colorectal distension after intracolonic instillation of MO. The effect of MO intracolonic sensitization was evaluated in intact rats, OVX rats, and OVX rats pretreated with a single injection of 17␤-estradiol (E), progesterone (P), EϩP, or vehicle. cAMPresponsive element-binding protein (CREB) and phosphorylated CREB (pCREB) were detected in the superficial dorsal horn of L6 and S1 in MO or mineral oil-treated OVX rats with/without colorectal distension and estrogen replacement. The distal colorectum was removed for histological evaluation of inflammatory severity in MOtreated intact or OVX rats. The MO-treated rats had significantly higher visceromotor reflex than controls (enhanced visceral hypersensitivity), whereas OVX eliminated this hypersensitivity. After a single injection of E or EϩP, the rats rapidly restored MO-induced visceral hypersensitivity within 2 h. Estrogen also rapidly induced a dosedependent increase in pCREB expression in the superficial dorsal horn neurons in MO-treated, but not mineral oil-treated, OVX rats. The present study suggests that estrogen can rapidly modulate visceral hypersensitivity induced by MO intracolonic instillation in conscious female rats, which may involve spinal activation of the cAMP response element-mediated gene induction pathway.irritable bowel syndrome; spinal cord; cAMP-response element binding protein; gender VISCERAL PAIN IS A COMMON complaint frequently encountered in the daily practice of gastrointestinal clinics. Studies have shown women are more likely than men to report pain, have lower pain thresholds, and feel pain with greater intensity (6, 43). Some chronic visceral or musculoskeletal pain syndromes, such as irritable bowel syndrome (IBS), fibromyalgia, and temporomandibular disorders, are also female predominant (11,21,44). Even in Eastern society, gender differences in IBS have been reported (28). Similarly, female rats exhibit larger pain reactions than males to thermal stimuli or formalin testing (4, 38).Both human and animal studies suggest gender differences in pain processing; however, the roles of sex hormones in visceral pain modulation are conflicting. For example, ovariectomized (OVX) rats exhibit similar or reduced visceromotor reflex (VMR) to colorectal distension (CRD) compared with controls (7, 23), whereas visceral pain behaviors are greatly increased in OVX mice upon intracolonic capsaicin stimulation (41). Estrogen did not affect the VMR by uterine cervical distension in ...

Objective: To examine prospectively whether irritable bowel syndrome (IBS) or other variables-that is, psychiatric profiles, health-related quality of life (HRQoL) and clinical features-are associated with negative appendectomy (NA). Design: Longitudinal study. Setting: Inpatient and emergency service in a university-affiliated teaching hospital. Patients: 430 consecutive patients underwent emergent surgery for suspected appendicitis. Main outcome measures: Rome-II IBS questionnaire; the Hospital Anxiety and Depression Scale; the ShortForm 36 survey; the clinical, pathological and CT findings. Results: The NA group (n = 68, 15.8%) was younger, with female predominance, higher prevalence of Rome-II IBS, higher anxiety/depression scores and lower levels of HRQoL than the positive appendectomy group. The patients with NA tended to have atypical presentations (absence of migration pain/fever/muscle guarding), lower white cell count and percentage of polymorphonuclear cells (PMNC) and lower rate of CT scan usage than the positive group. After multiple logistic regression, IBS (OR 2.17; 95% CI 1.14 to 4.24), degree of anxiety (OR 1.12; 95% CI 1.02 to 1.49), absence of migrating pain (OR 3.43; 95% CI 1.90 to 5.95)/muscle guarding (OR 3.72; 95% CI 2.07 to 6.70), a lower PMNC percentage (,75%; OR 3.05; 95% CI 1.69 to 5.51) and no CT scan usage (OR 2.32; 95% CI 1.27 to 4.26) were found to be the independent factors in predicting NA. Conclusion: Both patient (IBS, anxiety, atypical presentation) and physician (low CT scan usage) factors are the independent determinants predicting NA. Physicians should be cautious before operating on or referring patients with IBS for appendectomy. CT scan should be considered in patients with suspected appendicitis, particularly in those with IBS and atypical clinical presentations.A cute appendicitis is the most common cause of an acute abdomen with at least 250 000 cases per year in the US. 1The life-time risk of appendectomy is 12.0% for men and 23.1% for women.2 Although clinical symptoms are often characteristic, a high rate of misdiagnosis, often referred to as negative appendectomy (NA), suggests otherwise. Several studies have shown that over 15% of appendectomies performed revealed no pathological evidence of appendicitis. [3][4][5][6]

Background & AimsIt remains unknown what the prevalence of minimal hepatic encephalopathy is in Taiwan, a highly endemic country for chronic viral hepatitis infection. It is also unclear whether abnormal serum cytokine levels can be indicative of the presence of minimal hepatic encephalopathy. We aimed to standardize the tests of psychometric hepatic encephalopathy score and predictive value of proinflammatory cytokines in minimal hepatic encephalopathy in Taiwan.Methods180 healthy subjects and 94 cirrhotic patients without a history of overt hepatic encephalopathy from a tertiary center were invited to participate in this cross-sectional study. Blood sampling for determination of serum levels of interleukin 6 and 18 and tumor necrosis factor-α was performed. Based on the normogram of psychometric hepatic encephalopathy score from healthy volunteers, patients with minimal hepatic encephalopathy were identified from the cirrhotic patients using the criterion of a psychometric hepatic encephalopathy score less than −4.ResultsIn the healthy subjects, age and education were predictors of subtests of psychometric hepatic encephalopathy score. Minimal hepatic encephalopathy was identified in 27 (29%) cirrhotic patients. Serum interleukin 6 level (OR = 6.50, 95% CI = 1.64–25.76, P = 0.008) was predictive of the presence of minimal hepatic encephalopathy after multivariate analysis.ConclusionsThe psychometric hepatic encephalopathy score can be a useful tool for detecting patients with minimal hepatic encephalopathy in Taiwan and around one third of cirrhotic outpatients fulfill this diagnosis. A high serum interleukin 6 level is predictive of the presence of minimal hepatic encephalopathy.

For 5G wireless communications, the 3GPP Narrowband Internet of Things (NB-IoT) is one of the most promising technologies, which provides multiple types of resource unit (RU) with a special repetition mechanism to improve the scheduling flexibility and enhance the coverage and transmission reliability. Besides, NB-IoT supports different operation modes to reuse the spectrum of LTE and GSM, which can make use of bandwidth more efficiently. The IoT application grows rapidly; however, those massive IoT devices need to operate for a very long time. Thus, the energy consumption becomes a critical issue. Therefore, NB-IoT provides discontinuous reception operation to save devices' energy. But, how to further reduce the transmission energy while ensuring the required ultra-reliability is still an open issue. In this paper, we study how to guarantee the reliable communication and satisfy the quality of service (QoS) while minimizing the energy consumption for IoT devices. We first model the problem as an optimization problem and prove it to be NP-complete. Then, we propose an energy-efficient, ultra-reliable, and low-complexity scheme, which consists of two phases. The first phase tries to optimize the default transmit configurations of devices which incur the lowest energy consumption and satisfy the QoS requirement. The second phase leverages a weighting strategy to balance the emergency and inflexibility for determining the scheduling order to ensure the delay constraint while maintaining energy efficiency. Extensive simulation results show that our scheme can serve more devices with guaranteed QoS while saving their energy effectively.