Roles of estrogen receptor-alpha in mediating life span: the hypothalamic deregulation hypothesis.

In several species caloric restriction (CR) extends life span. In this paper we integrate data from studies on CR and other sources to articulate the hypothalamic deregulation hypothesis by which estrogen receptor-alpha (ER-α) signaling in the hypothalamus and limbic system affects life span under the stress of CR in mammals. ER-α is one of two principal estrogen-binding receptors differentially expressed in the amygdala, hippocampus, and several key hypothalamic nuclei: the arcuate nucleus (ARN), preoptic area (POA), ventromedial nucleus (VMN), antero ventral periventricular nucleus (AVPV), paraventricular nucleus (PVN), supraoptic nucleus (SON), and suprachiasmatic nucleus (SCN). Estradiol signaling via ER-α is essential in basal level functioning of reproductive cycle, sexually receptive behaviors, physiological stress responses, as well as sleep cycle, and other nonsexual behaviors. When an organism is placed under long-term CR, which introduces an external stress to this ER-α signaling, the reduction of ER-α expression is attenuated over time in the hypothalamus. This review paper seeks to characterize the downstream effects of ER-α in the hypothalamus and limbic system that affect normal endocrine functioning

Safety and Immunogenicity of Different Immunization Regimens of CVD 103-HgR Live Oral Cholera Vaccine in Soldiers and Civilians in Thailand

Attenuated Vibrio cholerae oral vaccineCVD 103-HgR was well tolerated by 324 Thai soldiers and civilians. Most receiveda single 5 × 108 cfu dose, while 40 each receivedone or two 5 × 109 cfu doses. Vibriocidal antibody (the best correlate of immunity) seroconversion was lower in soldiers than civilians (P < .001). Increasing the vaccinedose to 5 × 109 cfu raised the geometric mean titer (P < .001).Asecond 5 × 109 cfu dose one weeklater did not notably increase seroconversions. Likelihood of seroconversionwas inverselycorrelated with baseline vibriocidal titer (P < .001). CVD 103-HgR caused seroconversion in most subjects with baseline titers ⩽1:40, including 100% of civilians after one 5 × 108 cfu dose, 79% of soldiers after one 5 × 109 cfu dose, and 45% of soldiers after one 5 × 108 cfu dose. In persons with elevatedbaseline titers, vibriocidal antibody seroconversion is not a sensitive measure of whether vaccine has boosted intestinal immunity; for such subjects,other measurements must be used. Study regimens in endemic areas should use a single 5 × 109 cfu dos

Civilian-military malaria outbreak response in Thailand: an example of multi-stakeholder engagement for malaria elimination

Background In April 2017, the Thai Ministry of Public Health (MoPH) was alerted to a potential malaria outbreak among civilians and military personnel in Sisaket Province, a highly forested area bordering Cambodia. The objective of this study was to present findings from the joint civilian-military outbreak response. Methods A mixed-methods approach was used to assess risk factors among cases reported during the 2017 Sisaket malaria outbreak. Routine malaria surveillance data from January 2013 to March 2018 obtained from public and military medical reporting systems and key informant interviews (KIIs) (n = 72) were used to develop hypotheses about potential factors contributing to the outbreak. Joint civilian-military response activities included entomological surveys, mass screen and treat (MSAT) and vector control campaigns, and scale-up of the “1–3–7” reactive case detection approach among civilians alongside a pilot “1–3–7” study conducted by the Royal Thai Army (RTA). Results Between May–July 2017, the monthly number of MoPH-reported cases surpassed the epidemic threshold. Outbreak cases detected through the MoPH mainly consisted of Thai males (87%), working as rubber tappers (62%) or military/border police (15%), and Plasmodium vivax infections (73%). Compared to cases from the previous year (May–July 2016), outbreak cases were more likely to be rubber tappers (OR = 14.89 [95% CI: 5.79–38.29]; p \u3c 0.001) and infected with P. vivax (OR=2.32 [1.27–4.22]; p = 0.006). Themes from KIIs were congruent with findings from routine surveillance data. Though limited risk factor information was available from military cases, findings from RTA’s “1–3–7” study indicated transmission was likely occurring outside military bases. Data from entomological surveys and MSAT campaigns support this hypothesis, as vectors were mostly exophagic and parasite prevalence from MSAT campaigns was very low (range: 0-0.7% by PCR/microscopy). Conclusions In 2017, an outbreak of mainly P. vivax occurred in Sisaket Province, affecting mainly military and rubber tappers. Vector control use was limited to the home/military barracks, indicating that additional interventions were needed during high-risk forest travel periods. Importantly, this outbreak catalyzed joint civilian-military collaborations and integration of the RTA into the national malaria elimination strategy (NMES). The Sisaket outbreak response serves as an example of how civilian and military public health systems can collaborate to advance national malaria elimination goals in Southeast Asia and beyond

Civilian-military malaria outbreak response in Thailand: an example of multi-stakeholder engagement for malaria elimination.

BACKGROUND: In April 2017, the Thai Ministry of Public Health (MoPH) was alerted to a potential malaria outbreak among civilians and military personnel in Sisaket Province, a highly forested area bordering Cambodia. The objective of this study was to present findings from the joint civilian-military outbreak response. METHODS: A mixed-methods approach was used to assess risk factors among cases reported during the 2017 Sisaket malaria outbreak. Routine malaria surveillance data from January 2013 to March 2018 obtained from public and military medical reporting systems and key informant interviews (KIIs) (n = 72) were used to develop hypotheses about potential factors contributing to the outbreak. Joint civilian-military response activities included entomological surveys, mass screen and treat (MSAT) and vector control campaigns, and scale-up of the "1-3-7" reactive case detection approach among civilians alongside a pilot "1-3-7" study conducted by the Royal Thai Army (RTA). RESULTS: Between May-July 2017, the monthly number of MoPH-reported cases surpassed the epidemic threshold. Outbreak cases detected through the MoPH mainly consisted of Thai males (87%), working as rubber tappers (62%) or military/border police (15%), and Plasmodium vivax infections (73%). Compared to cases from the previous year (May-July 2016), outbreak cases were more likely to be rubber tappers (OR = 14.89 [95% CI: 5.79-38.29]; p < 0.001) and infected with P. vivax (OR=2.32 [1.27-4.22]; p = 0.006). Themes from KIIs were congruent with findings from routine surveillance data. Though limited risk factor information was available from military cases, findings from RTA's "1-3-7" study indicated transmission was likely occurring outside military bases. Data from entomological surveys and MSAT campaigns support this hypothesis, as vectors were mostly exophagic and parasite prevalence from MSAT campaigns was very low (range: 0-0.7% by PCR/microscopy). CONCLUSIONS: In 2017, an outbreak of mainly P. vivax occurred in Sisaket Province, affecting mainly military and rubber tappers. Vector control use was limited to the home/military barracks, indicating that additional interventions were needed during high-risk forest travel periods. Importantly, this outbreak catalyzed joint civilian-military collaborations and integration of the RTA into the national malaria elimination strategy (NMES). The Sisaket outbreak response serves as an example of how civilian and military public health systems can collaborate to advance national malaria elimination goals in Southeast Asia and beyond

Roles of estrogen receptor-alpha in mediating life span: the hypothalamic deregulation hypothesis.

In several species caloric restriction (CR) extends life span. In this paper we integrate data from studies on CR and other sources to articulate the hypothalamic deregulation hypothesis by which estrogen receptor-alpha (ER-α) signaling in the hypothalamus and limbic system affects life span under the stress of CR in mammals. ER-α is one of two principal estrogen-binding receptors differentially expressed in the amygdala, hippocampus, and several key hypothalamic nuclei: the arcuate nucleus (ARN), preoptic area (POA), ventromedial nucleus (VMN), antero ventral periventricular nucleus (AVPV), paraventricular nucleus (PVN), supraoptic nucleus (SON), and suprachiasmatic nucleus (SCN). Estradiol signaling via ER-α is essential in basal level functioning of reproductive cycle, sexually receptive behaviors, physiological stress responses, as well as sleep cycle, and other nonsexual behaviors. When an organism is placed under long-term CR, which introduces an external stress to this ER-α signaling, the reduction of ER-α expression is attenuated over time in the hypothalamus. This review paper seeks to characterize the downstream effects of ER-α in the hypothalamus and limbic system that affect normal endocrine functioning

Fluorescence Polarization Measurements to Probe Alignment of a Bithiophene Dye in One-Dimensional Channels of Self-Assembled Phenylethynylene Bis-Urea Macrocycle Crystals

This paper describes the use of polarized fluorescence microscopy to directly probe guest molecule orientation in bis-urea macrocycle crystals. These macrocycles assemble to afford one-dimensional (1D) microchannels ∼9 Å in diameter that have previously been shown to exhibit normal Fickian diffusion and induce selective reactivity among the confined guest molecules. In the present work, we take advantage of the quasi-1D morphology of fiber-like microcrystals with the extended dimension corresponding to the channel axis to measure excitation and emission polarization values for a bithiophene guest. Guest fluorescence is shown to be polarized along the fiber axis with emission polarization values up to 0.729, indicating a high degree of orientational order within the 1D channels. The observed behavior is consistent with calculated results for the guest orientation and electronic transition dipole moment. The results indicate the value of functional fluorescent probes as a measure of guest confinement in low-dimensional environments

Civilian-military malaria outbreak response in Thailand: an example of multi-stakeholder engagement for malaria elimination.

BackgroundIn April 2017, the Thai Ministry of Public Health (MoPH) was alerted to a potential malaria outbreak among civilians and military personnel in Sisaket Province, a highly forested area bordering Cambodia. The objective of this study was to present findings from the joint civilian-military outbreak response.MethodsA mixed-methods approach was used to assess risk factors among cases reported during the 2017 Sisaket malaria outbreak. Routine malaria surveillance data from January 2013 to March 2018 obtained from public and military medical reporting systems and key informant interviews (KIIs) (n = 72) were used to develop hypotheses about potential factors contributing to the outbreak. Joint civilian-military response activities included entomological surveys, mass screen and treat (MSAT) and vector control campaigns, and scale-up of the "1-3-7" reactive case detection approach among civilians alongside a pilot "1-3-7" study conducted by the Royal Thai Army (RTA).ResultsBetween May-July 2017, the monthly number of MoPH-reported cases surpassed the epidemic threshold. Outbreak cases detected through the MoPH mainly consisted of Thai males (87%), working as rubber tappers (62%) or military/border police (15%), and Plasmodium vivax infections (73%). Compared to cases from the previous year (May-July 2016), outbreak cases were more likely to be rubber tappers (OR = 14.89 [95% CI: 5.79-38.29]; p &lt; 0.001) and infected with P. vivax (OR=2.32 [1.27-4.22]; p = 0.006). Themes from KIIs were congruent with findings from routine surveillance data. Though limited risk factor information was available from military cases, findings from RTA's "1-3-7" study indicated transmission was likely occurring outside military bases. Data from entomological surveys and MSAT campaigns support this hypothesis, as vectors were mostly exophagic and parasite prevalence from MSAT campaigns was very low (range: 0-0.7% by PCR/microscopy).ConclusionsIn 2017, an outbreak of mainly P. vivax occurred in Sisaket Province, affecting mainly military and rubber tappers. Vector control use was limited to the home/military barracks, indicating that additional interventions were needed during high-risk forest travel periods. Importantly, this outbreak catalyzed joint civilian-military collaborations and integration of the RTA into the national malaria elimination strategy (NMES). The Sisaket outbreak response serves as an example of how civilian and military public health systems can collaborate to advance national malaria elimination goals in Southeast Asia and beyond