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We compared clinical outcomes between patients with healthcare-associated and community-acquired Klebsiella pneumoniae bacteraemia and identified predictors associated with mortality and high treatment cost in Hong Kong.This was a retrospective cohort study of patients with K. pneumoniae bacteraemia in a teaching hospital. Adult patients with K. pneumoniae in blood cultures were included. Demographics and clinical data were retrieved from medical records.The analysis included 208 patients. The mean age was 68.6 ± 16.8 years. The Pitt bacteraemia score was 2.2 ± 2.8. In all, 54.8% cases were healthcare-associated infections. The 30-day mortality rate was 32.7%. The mortality rate of patients with healthcare-associated bacteraemia was significantly higher than for community-acquired cases (p0.001). Extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae accounted for 15.4% of cases. Intra- abdominal infection was the most common infection (32.7%). Prior use of immunosuppressive agents and antimicrobial therapy were two major predisposing factors for infection. The treatment cost was USD12 282 ± 11 751 and the length of hospitalization was 9.0 ± 6.7 days. Multivariate analysis showed that liver disease (odds ratio (OR) = 3.06; 95% confidence interval (CI) = 1.38-6.78), malignancy (OR = 6.86; 95% CI = 3.25-14.48), pneumonia (OR = 5.25; 95% CI = 2.05-13.41) and Pitt score1 (OR = 2.50; 95% CI = 1.25-5.00) were associated with mortality. Malignancy (OR = 2.94; 95% CI = 1.33-6.49), Pitt score1 (OR = 4.15; 95% CI = 1.87-9.24) and age72 years (OR = 2.86; 95% CI = 1.35-5.88) were associated with high treatment cost.The 30-day mortality and treatment cost of patients with K. pneumoniae bacteraemia were high in Hong Kong. Based upon the risk factors identified, infection control and treatment algorithms for K. pneumoniae bacteraemia in patients with malignancy or liver disease are highly warranted.

Self-reported measurements of attentional bias are possibly influenced by social desirability, conscious awareness, or introspection. This study developed a visual dot-probe task to study the relationship between attentional bias and posttraumatic stress disorder among women with breast cancer. Fifty six women with breast cancer were presented with a series of face pairs, which were equally divided into positive-neutral and negative-neutral pairs. One face pair was shown for each trial, which consisted of the neutral and emotional versions of the same face displaying side-toside. Participants’ goal was to detect a small dot displayed on the screen after disappearance of the faces as quickly as possible in 80 trials. Negative/positive attentional bias was the mean latency to detect probes appearing on the side of neutral faces minus that of negative/positive faces. We investigated the relationships between the dot-probe task and the Chinese Impact of Event Scale (CIES-R) and demographic variables. Negative attentional bias as measured by the dot-probe task was positively correlated with the CIES-R total score ( r = 0.30, p< 0.05), the hyperarousal subscale (r = 0.32, p< 0.05), and the intrusions subscale ( r = 0.30, p< 0.05) but not the avoidance subscale ( r = 0.32, p = 0.14). This study has demonstrated that measuring attentional bias with a dot-probe task is possible. The dot-probe task may provide an alternative measurement to self-reported measurements and important information for psychotherapies. Future studies may examine the predictive values of the dot-probe task on treatment outcomes and the risk for developing symptoms of post-traumatic stress disorder.

Background We performed a pilot evaluation of a new formulation of levonorgestrel butanoate (LB) designed to be a long-acting injectable (6 months) contraceptive to determine pharmacodynamic end points in normal-body mass index (BMI) and obese women. Study design Obese (BMI ≥30 kg/m 2 ) and normal-BMI, otherwise healthy, women received a single intramuscular injection of LB after ovulation was confirmed in a baseline cycle. The primary outcome was return of ovulation in days. Results A total of 14 women enrolled and completed the study [normal BMI n =9, median BMI 22.7kg/m 2 (range 19.4–25.8); obese n =5, median BMI 35.7kg/m 2 (30.1–39.2)]. The first 6 subjects (normal BMI=4/9, obese BMI=2/5) received 40 mg of LB, and the remaining 8 received 20 mg. All women except one returned to ovulation prior to 6 months. Return to ovulation occurred earlier in the obese group; 3/5 obese and 0/9 normal BMI subjects returned to ovulation within 90 days (p=.03). No serious adverse events were reported during the study. Conclusion Return to ovulation was earlier than 6 months in both BMI groups but more so in the obese BMI group. Implications Since return of ovulation was earlier than expected for this LB injectable formulation, additional steps are needed to develop a preparation suitable as a longer-lasting product.

Hyperandrogenemia is associated with several clinical disorders in which both reproductive dysfunction and metabolic changes may coexist [i.e. polycystic ovary syndrome (PCOS), obesity and congenital adrenal hyperplasia]. Moreover, there is growing evidence that the elevated levels of circulating androgens in obese girls may lead to an increased neuroendocrine drive to the reproductive axis, similar to that associated with PCOS.To test whether androgen exposure in the childhood and adolescent period could lead to pubertal alterations in LH secretory patterns, female rhesus monkeys received subcutaneous testosterone implants prepubertally beginning at 1 year of age, maintaining a 3.7-fold increase (P = 0.001) in circulating testosterone levels over cholesterol-implant controls (n = 6/group) into the post-pubertal period. In early adulthood, pulsatile secretion of LH was measured over 12 h during the early follicular phase of a menstrual cycle, and responsiveness of the pituitary to gonadotrophin-releasing hormone was determined. In addition, ultrasounds were performed to assess ovarian morphology and glucose tolerance testing was performed to assess insulin sensitivity.The timing of menarche was similar between groups. Testosterone-treated animals had a significantly greater LH pulse frequency during the early follicular phase compared with controls (P = 0.039) when measured at 5 years of age. There was a larger LH response to GnRH when testosterone-treated animals were 4 years of age (P = 0.042), but not when the animals were 5 years old (P = 0.57). No differences were seen in insulin sensitivity or ovarian morphology, and the groups showed similar rates of ovulation in early adulthood.Exposure to increased levels of androgens over the course of pubertal development appears to trigger physiological changes in the neural drive to the reproductive axis that resemble those of obese hyperandrogenemic girls in early adulthood and are characteristic of PCOS.

Rabbit does nurse their litter once every 24 h during the night. We hypothesized that corticosterone, ghrelin, leptin, and metabolites such as glucose, liver glycogen, and free fatty acids could be affected in the pups by the time at which does nurse them. Therefore, we measured these parameters in pups nursed at 02:00 h (nighttime for the doe) to compare them with results from a previous study where does nursed at 10:00 h, during daytime. From postnatal day 7, pups were sacrificed either just before their scheduled time of nursing or at 4, 8, 12, 16, or 20 h after nursing ( n = 6 at each time point); additional pups were sacrificed at 4 h intervals between 48 and 72 h after nursing to study the persistence of oscillations during fasting. All pups developed locomotor anticipatory activity to nursing. Corticosterone, ghrelin, and free fatty acids exhibited a rhythm that persisted in fasted pups. Glucose concentrations were lower in fasted than in nursed pups, and glycogen was only detected in nursed subjects. Leptin values were stable and low in nursed subjects but increased significantly in fasted subjects up to 72 h after the expected nursing time. The rhythm of ghrelin persisted during fasting, contrary to our previous findings in pups nursed during daytime (i.e., outside the natural time of nursing for this species). Therefore, in 7-day-old rabbit pups, night nursing is a strong zeitgeber for corticosterone, ghrelin, free fatty acids, and energy metabolites but not for leptin.

Anxiety is a normal aspect of human personality, which can manifest in a variety of disorders and other negative traits. The primary treatment for anxiety is the class of drugs known as the selective serotonin reuptake inhibitors (SSRIs), which bind to the serotonin reuptake transporter. The upstream region of the gene that codes for this transporter contains a polymorphism that is an insertion/deletion event that in turn, produces long (l) and short (s) alleles in the population. This particular polymorphism in the serotonin transporter, the 5HTTLPR (serotonin transporter linked polymorphic region), is thought to be involved in the genesis of anxious traits and disorders. Most studies with human subjects have examined adult behavior, which may derive from diverse experiential and environmental backgrounds, as well as genetic differences. To better isolate the effect of genetics, we genotyped 128 infant and juvenile monkeys for the 5HTTLPR and tested for behavioral response in four testing paradigms designed to elicit fearful-anxious behaviors: a free play, remote-controlled car, human intruder, and novel fruit test. The s/s monkeys were found to be behaviorally inhibited in the free play test, engaged in more fear behaviors in the remote-controlled car test, and threatened more in the stare portion of the human intruder test, even though a small number of monkeys were assessed. There was no difference between genotypes of either sex in the prolactin response to fenfluramine. These data indicate greater anxiety in the s/s monkeys for distinct facets of anxious behavior, which are independent of a global neurohormonal challenge test. These neurobehavioral data support recent neuroimaging findings in humans indicating the importance of the 5HTTLPR for amygdala-dependent anxious behavior.

Many patients with hyperandrogenemia are overweight or obese, which exacerbates morbidities associated with polycystic ovary syndrome (PCOS). To examine the ability of testosterone (T) to generate PCOS-like symptoms, monkeys received T or cholesterol (control) implants ( n = 6/group) beginning prepubertally. As previously reported, T-treated animals had increased neuroendocrine drive to the reproductive axis [increased luteinizing hormone (LH) pulse frequency] at 5 yr, without remarkable changes in ovarian or metabolic features. To examine the combined effects of T and obesity, at 5.5 yr (human equivalent age: 17 yr), monkeys were placed on a high-calorie, high-fat diet typical of Western cultures [Western style diet (WSD)], which increased body fat from

The annual killifish, Austrofundulus limnaeus, typically enters embryonic diapause at two distinct points of development, termed diapause II and III. This study explores the role of maternal and embryonic steroid hormones, including 17-β-estradiol (E2), androstenedione (A4) and testosterone (T), in regulating the developmental decision to enter or escape diapause II. Steroid hormone levels were measured in tissues isolated from adult female killifish during the normal lifespan of this species and in individuals of the same age that were producing either high or low proportions of escape embryos. Levels of steroid hormones were also measured during early development and in fertilized eggs that were predicted to be on either an escape or diapausing developmental trajectory. Decreases in maternal E2 levels associated with age are correlated with decreasing escape embryo production. Maternal production of escape embryos is correlated with increased ratios of E2 to T in adult ovary tissue. Interestingly, neither hormone is significantly different in fish producing embryos on different developmental pathways when examined independently. Levels of steroid hormones in fertilized eggs are not correlated with entry or escape from diapause II, though levels of A4 tend to be higher in escape embryos. Escape embryos exhibit faster hormone metabolism and earlier hormone synthesis than embryos that will enter diapause II. Incubation of embryos in exogenous E2 is associated with a 7-fold increase in escape embryo production, and significantly elevated A4 levels. These data suggest that steroid hormones may be critical factors involved in determining developmental pathways in embryos of A. limnaeus.

Objective To use a nonhuman primate model and determine whether individuals sensitive to stress-induced reproductive dysfunction have lower activity of central serotonergic neurons under nonstressed conditions. Design The activity of the central serotonergic system was assessed by measuring responsiveness to a fenfluramine challenge (5 mg/kg, IV) in sedated monkeys previously categorized as highly stress resistant (HSR; n=4; normal menstrual cyclicity through two stress cycles), medium stress resistant (MSR; n=5; ovulatory in the first stress cycle but anovulatory in the second stress cycle), or low stress resistant (i.e., stress sensitive, SS; n=4; anovulatory as soon as stress is initiated). To control for differences in pituitary stores of prolactin or ACTH, the animals were subsequently administered a bolus of thyrotropin-releasing hormone (3 μg/kg) plus corticotropin releasing factor (CRF), (3 μg/kg). Setting Oregon National Primate Research Center, Animal Services Building. Patient(s) Female cynomolgus macaques exhibiting normal menstrual cycles. Intervention(s) Administration of fenfluramine, a serotonin-releasing drug. Main outcomes measure(s) Serum concentrations of prolactin (PRL) and cortisol (F). Result(s) Prolactin release in response to fenfluramine was significantly greater in the HSR group compared with the MSR or SS groups. In contrast, cortisol was higher in the SS group compared with the other two groups. Similar responses were not evident after thyrotropin-releasing hormone + CRF stimulation. Conclusion(s) The lower PRL response to fenfluramine in the stress-sensitive animals suggests that stress-sensitive individuals have decreased activity in central serotonergic neurons. However, the F data suggest that the hypothalamic-pituitary-adrenal axis in stress-sensitive individuals is highly responsive to even small increases in serotonin.