Procalcitonin, a valuable biomarker assisting clinical decision-making in the management of community-acquired pneumonia.

BACKGROUND AND AIM: Community-acquired pneumonia (CAP) is a leading cause of mortality, morbidity and hospital admission, which places strain on our healthcare system. Procalcitonin (PCT) is a biomarker of bacterial infection which may help gauge the severity and prognosis of patients with CAP. In addition to clinical predictors, PCT may assist in decisions pertaining to timing of discharge from hospital and the discontinuation of antibiotics. This study aimed to determine the predictive role of PCT measurement in reducing hospital admissions, length of stay (LOS) and antibiotic (AB) usage in patients with CAP. METHODS: A prospective, single-blinded, externally controlled study of consenting adult patients admitted with CAP. PCT levels were obtained on day 1 and day 3 (when indicated). Investigator-evaluated clinical parameters, together with results of PCT levels, determined the timing of oral AB switch and discharge from hospital. This process was compared against standard practice, but was not actually implemented, for the purpose of this study. RESULTS: Sixty patients were included in the study. The mean age was 66.5 ± 21.2 years (56.3% male). The average Pneumonia Severity Index was 93 ± 39 (class IV) and the median CURB-65 was 2. The mean LOS for the standard practice cohort was 5.3 ± 4.6 days versus calculated LOS using the PCT guidance pathway of 3.7 ± 2.8 days. (P = 0.00006). CONCLUSIONS: Our study supports the hypothesis that by incorporation of PCT levels, hospital admission and LOS in patients with CAP can be reduced. A randomised prospective clinical trial is planned in an attempt to help confirm these findings.

Excess mortality and suicide risk in treatment-seeking individuals with schizotypal disorder: A population-based study using Swedish national registers.

This study investigates the excess mortality, both all-cause and due to suicide, among individuals with schizotypal disorder (SD) compared to the general population. Using individual-level data from the Swedish National Patient Register and the Cause of Death Register, we analyzed mortality in 998 patients diagnosed with SD from 2006 to 2017. Our primary outcomes were all-cause mortality and suicide mortality, with baseline variables including sex, age, and psychiatric comorbidities. Results indicated significantly elevated mortality rates for both all-cause mortality (Standardized Mortality Ratio (SMR) 5.2) and suicide (SMR 23.4). Substance use disorders, personality disorders, and ADHD were identified as significant predictors of increased all-cause mortality. Notably, having a personality disorder in conjunction with schizotypal disorder resulted in a markedly increased risk of suicide. The study underscores the urgent need for targeted interventions and improved diagnostic precision to reduce premature mortality in this vulnerable population. Additionally, the relatively low prevalence of SD diagnoses in Sweden highlights a potential underdiagnosis or misclassification issue. These findings have critical implications for clinical practice and public health efforts, emphasizing the necessity for comprehensive care strategies and suicide prevention interventions to improve outcomes for individuals with schizotypal disorder.

Impact of the 2009 Melbourne heatwave on a major public hospital.

In the week following the onset of the 2009 heatwave in Melbourne, Australia, The Alfred Hospital observed a significant increase in total hospital admissions (adjusted incidence rate ratio (IRR) 1.11, P = 0.046), emergency department presentations (IRR 1.15, P < 0.01) and general medical admissions (IRR 1.81, P < 0.01). Under the general medical unit there was a rise in the number of deaths (IRR 3.9, P < 0.01), and patients with a broad range of disorders, particularly of the endocrine/metabolic (IRR 2.2, P < 0.01), circulatory (IRR 1.9, P < 0.01) and genitourinary (IRR 2.6, P < 0.01) systems.

The Influence of Treatment Latency on Suicide-Specific Treatment Outcomes.

INTRODUCTION: The Attempted Suicude Short Intervention Program (ASSIP) provides an effective and cost-effective treatment option for people who have attempted suicide. Studies suggest that longer treatment latency is associated with poorer response to therapy, more severe symptomatology, and more suicide attempts This study examined the influence of treatment latency (time between suicide attempt and initiation of therapy) on the number of suicide attempts over the long-term course of ASSIP and the influence of treatment relationship on the extent of suicidal ideation. METHOD: Survival and regression analyses were performed on 60 participants who had recently attempted suicide and received ASSIP at an outpatient psychiatric clinic. 60% were women and 40% were men. RESULTS: The results found no significant association between treatment outcome in ASSIP and treatment latency (HR = 1.06; 95% CI: 0.92- 1.21, p = .44). Treatment relationship significantly influenced suicidal ideation at time t4 (B = - .35, t(55) = -3.21, p = .002), but treatment latency was not significantly associated with suicidal ideation (B = .02, t(55) = 0.87, p = .39). CONCLUSION: No relationship between treatment latency and treatment outcome could be found, suggesting that ASSIP can be implemented at any time after the last suicide attempt. In contrast, the treatment relationship plays a central role in ASSIP.

Veno-right ventricular cannulation reduces recirculation in extracorporeal membrane oxygenation.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation has several advantages over veno-arterial support for patients with severe reversible respiratory failure. However, recirculation can limit oxygen delivery as pump flow increases. This could be ameliorated by placing the return catheter in the right ventricle instead of the central veins. We compared recirculation in veno-right ventricular support with that in conventional veno-venous support and its relationship with pump flow. METHODS: Five greyhound dogs were sequentially cannulated percutaneously for both veno-venous and veno-right ventricular support. Recirculation was measured by comparing oxygen levels in the circuit drainage and return lines before and immediately after a sudden increase in circuit oxygenation at pump flows between 0.5 L/min and 4 L/min for both modalities. RESULTS: Recirculation was reduced in veno-right ventricular support compared with conventional veno-venous support at 4 L/min pump flow (8.4% versus 37.9%, p=0.0076) and increased less with increases in pump flow (2.9% per 1 L/min vs. 11.1% per 1 L/min, p<0.0001). CONCLUSIONS: Recirculation can be dramatically reduced by returning blood into the right ventricle, which improves oxygen delivery to the lungs and the systemic circulation. The design of specialized catheters may facilitate percutaneous ventricular cannulation, improve safety and further reduce recirculation.

Detecting 2009 pandemic influenza A (H1N1) virus infection: availability of diagnostic testing led to rapid pandemic response.

Diagnostic tests for detecting emerging influenza virus strains with pandemic potential are critical for directing global influenza prevention and control activities. In 2008, the Centers for Disease Control and Prevention received US Food and Drug Administration approval for a highly sensitive influenza polymerase chain reaction (PCR) assay. Devices were deployed to public health laboratories in the United States and globally. Within 2 weeks of the first recognition of 2009 pandemic influenza H1N1, the Centers for Disease Control and Prevention developed and began distributing a new approved pandemic influenza H1N1 PCR assay, which used the previously deployed device platform to meet a >8-fold increase in specimen submissions. Rapid antigen tests were widely used by clinicians at the point of care; however, test sensitivity was low (40%-69%). Many clinical laboratories developed their own pandemic influenza H1N1 PCR assays to meet clinician demand. Future planning efforts should identify ways to improve availability of reliable testing to manage patient care and approaches for optimal use of molecular testing for detecting and controlling emerging influenza virus strains.

Study of compliance with a clinical pathway for suspected pulmonary embolism.

BACKGROUND/AIMS: Clinical pathways to guide the investigation of suspected pulmonary embolism have been increasingly adopted by emergency departments worldwide. This study evaluated the compliance with a clinical pathway that combines risk assessment (Wells score) with d-dimer, ventilation-perfusion scanning or computed tomographic pulmonary angiography (CTPA). The aims of this study were to identify factors that contribute to compliance and to assess patient outcomes and resource utilization. METHODS: Repeated retrospective chart reviews of 239 patients who underwent investigation for pulmonary embolism through our emergency department extracted patient demographics, pathway parameters and patient outcomes. A phone interview at 3-month follow up was carried out. RESULTS: Incidence of pulmonary embolism was 8.4% (n= 20). Compliance to the clinical pathway occurred in 120 subjects (50.2%). Non-compliance occurred in 71 subjects (29.7%). Forty-eight subjects (20.1%) underwent risk assessments, but subsequent diagnostic tests did not conform to the stated pathway (partial compliance). Compliance was poor in subjects assessed by non-emergency department doctors (χ(2) = 27.95, P≤ 0.001). Compliance occurred less in pregnant subjects (χ(2) = 7.27, P= 0.007) and those with chronic respiratory disease (χ(2) = 5.31, P= 0.021). Subjects in the compliant group were less likely to undergo CTPA (odds ratio 2.07 (1.16-3.70), P= 0.012). CONCLUSIONS: Compliance with this clinical pathway allowed emergency department doctors in an Australian university teaching hospital to complete diagnostic testing for suspected pulmonary embolism appropriately unless non-emergency department doctors became involved. Compliance with this pathway altered the distribution of diagnostic tests performed with less reliance on CTPA, but was not associated with better patient outcomes.

Distribution and structure of efferent synapses in the chicken retina.

The visual system of birds includes an efferent projection from a visual area, the isthmo-optic nucleus in the midbrain, back to the retina. Using a combination of anterograde labeling of efferent fibers, reconstruction of dye-filled neurons, NADPH-diaphorase staining, and transmission electron microscopy, we have examined the distribution of efferent fibers and their synaptic structures in the chicken retina. We show that efferent fibers terminate strictly within the ventral retina. In two completely mapped retinas, only 2 fibers from a total of 15,359 terminated in the dorsal retina. The major synapse made by each efferent fiber is with a single efferent target amacrine cell (TC). This synapse consists of 5-25 boutons of 2 microm diameter, each with multiple active zones, pressed into the TC soma or synapsing with a basketwork of rudimentary TC dendrites in the inner nuclear layer (INL). This basketwork, which is sheathed by Muller cell processes, defines a private neuropil in the INL within which TCs were also seen to receive input from retinal neurons. In addition to the major synapse, efferent fibers typically produce several very thin processes that terminate nearby in single small boutons and for which the soma of a local amacrine cell is one of the likely postsynaptic partners. A minority of efferent fibers also give rise to a thicker process, terminating in a strongly diaphorase-positive ball about 5 microm in diameter.

Night-time diuresis pattern in children with and without primary monosymptomatic nocturnal enuresis.

INTRODUCTION: Night-time polyuria as the dominating pathophysiological mechanism for primary monosymptomatic nocturnal enuresis (PMNE) has been put in question with nocturnal detrusor overactivity and high arousal thresholds as alternatives. An earlier finding of night-time polyuria in 12% of healthy non-enuretic schoolchildren underscores that excessive night-time diuresis per se is unlikely the major cause of PMNE. OBJECTIVE: The objective of this study was to compare the night-time diuresis pattern in children with and without PMNE and to evaluate the role of night-time polyuria in provoking enuretic episodes in children with PMNE. STUDY DESIGN: Night-time diuresis pattern was recorded in 27 children with PMNE, aged 6-15 years, and 29 non-enuretic children, aged 6-13 years. Using a portable ultrasound recorder, the bladder volume was estimated at 15-min intervals for at least three nights with the child sleeping in its own bed at home. The volume of enuretic episodes was controlled using preweighed diapers. All voids were registered by time and volume. Diuresis during night time was estimated from the slope of regression lines fitted to ultrasound recording points. Mean night-time diuresis was calculated from total urine production during the night and time interval from the last void before bedtime to the first morning void. RESULTS: Night-time bladder filling pattern was recorded from 189 nights, giving 149 interpretable patterns for analysis (77 children with PMNE and 72 dry children). The night-time diuresis pattern was similar for children with or without PMNE, showing large variability between different nights of the same child. Most nights displayed a smooth bladder filling at constant low rate, whereas other nights showed an early phase with high diuresis followed by a longer period of low diuresis with no difference between the two groups. DISCUSSION: Night-time diuresis has been non-invasively monitored in children while asleep in their own beds at home. The pattern of night-time diuresis varies considerably between different nights of the same child, with no obvious differences in any diuresis parameters between children with or without PMNE. CONCLUSION: Non-enuretic children have similar diuresis pattern and maximal night-time diuresis values as children with PMNE, making it unlikely that PMNE is caused by night-time polyuria per se (Summary figure). Delayed maturation of sleep mechanisms such as decreased arousability or sleep inhibition of the micturition reflex is more likely to be the main etiology for enuresis.

Meta-analysis reveals that pollinator functional diversity and abundance enhance crop pollination and yield.

How insects promote crop pollination remains poorly understood in terms of the contribution of functional trait differences between species. We used meta-analyses to test for correlations between community abundance, species richness and functional trait metrics with oilseed rape yield, a globally important crop. While overall abundance is consistently important in predicting yield, functional divergence between species traits also showed a positive correlation. This result supports the complementarity hypothesis that pollination function is maintained by non-overlapping trait distributions. In artificially constructed communities (mesocosms), species richness is positively correlated with yield, although this effect is not seen under field conditions. As traits of the dominant species do not predict yield above that attributed to the effect of abundance alone, we find no evidence in support of the mass ratio hypothesis. Management practices increasing not just pollinator abundance, but also functional divergence, could benefit oilseed rape agriculture.

Alcohol consumption and the risk of incident pulmonary embolism in US women and men.

Essentials The association of moderate alcohol consumption with pulmonary embolism (PE) risk remains unclear. In three large US cohorts, we evaluated the association of alcohol consumption with PE risk. We found no evidence of an association of alcohol consumption amount or frequency with PE risk. Secondary analyses of type and heavy episodic drinking also yielded null findings. SUMMARY: Background Moderate alcohol consumption has been variably associated with hemostatic and fibrinolytic factor levels, but the association between alcohol consumption and the risk of incident pulmonary embolism (PE) remains uncertain. Objective To evaluate alcohol consumption amount and frequency in relation to PE risk. Methods Nurses' Health Study (NHS), NHS II and Health Professionals Follow-Up Study participants free of venous thromboembolism (VTE) at baseline (n = 217 442) reported alcohol consumption by type, quantity and frequency, every 2-4 years. Incident PE cases were identified by self-report and confirmed for participants without cancer. In this cohort study, we used Cox proportional hazards models to estimate multivariable-adjusted hazard ratios (HRs) for PE associated with alcohol consumption amount and, separately, frequency. Secondary analyses evaluated alcohol type and heavy episodic drinking in relation to PE risk, and amount and frequency in relation to medical record-confirmed idiopathic PE and any self-reported VTE risk. Cohort-specific analyses were pooled using random-effects meta-analysis. Results During ≥ 20 years of follow-up, we identified 1939 PE events. We found no strong evidence of an association between PE risk and alcohol consumption amount (pooled HRadj for 5.0-14.9 g day-1 vs. abstention = 0.97 [95% CI, 0.79, 1.20]) or frequency (pooled HRadj for 5-7 drinking days per week vs. abstention = 1.04 [95% CI, 0.88, 1.23]). Secondary analyses of type, heavy episodic drinking, idiopathic PE and VTE also yielded null findings. Conclusions Among three large prospective cohorts of US men and women, we found no evidence of an association between the amount or frequency of alcohol consumption and PE risk.

Metabolomic analysis of 92 pulmonary embolism patients from a nested case-control study identifies metabolites associated with adverse clinical outcomes.

Essentials Risk-stratification often fails to predict clinical deterioration in pulmonary embolism (PE). First-ever high-throughput metabolomics analysis of risk-stratified PE patients. Changes in circulating metabolites reflect a compromised energy metabolism in PE. Metabolites play a key role in the pathophysiology and risk stratification of PE. SUMMARY: Background Patients with acute pulmonary embolism (PE) exhibit wide variation in clinical presentation and outcomes. Our understanding of the pathophysiologic mechanisms differentiating low-risk and high-risk PE is limited, so current risk-stratification efforts often fail to predict clinical deterioration and are insufficient to guide management. Objectives To improve our understanding of the physiology differentiating low-risk from high-risk PE, we conducted the first-ever high-throughput metabolomics analysis (843 named metabolites) comparing PE patients across risk strata within a nested case-control study. Patients/methods We enrolled 92 patients diagnosed with acute PE and collected plasma within 24 h of PE diagnosis. We used linear regression and pathway analysis to identify metabolites and pathways associated with PE risk-strata. Results When we compared 46 low-risk with 46 intermediate/high-risk PEs, 50 metabolites were significantly different after multiple testing correction. These metabolites were enriched in the following pathways: tricarboxylic acid (TCA) cycle, fatty acid metabolism (acyl carnitine) and purine metabolism, (hypo)xanthine/inosine containing. Additionally, energy, nucleotide and amino acid pathways were downregulated in intermediate/high-risk PE patients. When we compared 28 intermediate-risk with 18 high-risk PE patients, 41 metabolites differed at a nominal P-value level. These metabolites were enriched in fatty acid metabolism (acyl cholines), and hemoglobin and porphyrin metabolism. Conclusion Our results suggest that high-throughput metabolomics can provide insight into the pathophysiology of PE. Specifically, changes in circulating metabolites reflect compromised energy metabolism in intermediate/high-risk PE patients. These findings demonstrate the important role metabolites play in the pathophysiology of PE and highlight metabolomics as a potential tool for risk stratification of PE.

The initial stage of reversal learning is impaired in mice hemizygous for the vesicular glutamate transporter (VGluT1).

Behavioral flexibility is a complex cognitive function that is necessary for survival in changeable environments. Patients with schizophrenia or Parkinson's disease often suffer from cognitive rigidity, reducing their capacity to function in society. Patients and rodent models with focal lesions in the prefrontal cortex (PFC) show similar rigidity, owing to the loss of PFC regulation of subcortical reward circuits involved in behavioral flexibility. The vesicular glutamate transporter (VGluT1) is preferentially expressed at modulatory synapses, including PFC neurons that project to components of the reward circuit (such as the nucleus accumbens, NAc). VGluT1(+/-) mice display behavioral phenotypes matching many symptoms of schizophrenia, and VGluT1 expression is reduced in the PFC of patients with schizophrenia and Parkinson's disease. Thus, it appears likely that VGluT1-expressing synapses from PFC play a key role in behavioral flexibility. To examine this hypothesis, we studied behavioral flexibility in VGluT1(+/-) mice by testing reversal learning in a visual discrimination task. Here, we show that VGluT1(+/-) mice acquired the initial visual discrimination at the same rate as controls. However, they failed to suppress responses to the previously rewarded stimulus following reversal of reward contingencies. Thus, our genetic disruption of modulatory glutamatergic signaling, including that arising from PFC, appears to have impaired the first stage of reversal learning (extinguishing responses to previously rewarded stimuli). Our data show that this deficit stems from a preservative phenotype. These findings suggest that glutamatergic regulation from the cortex is important for behavioral flexibility and the disruption of this pathway may be relevant in diseases such as schizophrenia.

Pulsatile secretion of luteinizing hormone during the menstrual cycle of rhesus macaques.

The secretion of LH, PRL, and cortisol was investigated in 4 sexually mature female rhesus macaques with cardiac catheters protected by tethers. Based on endocrine parameters, all 4 of the animals ovulated within 2 months from the time they were tethered, and regular menstrual cycles of 24-34 days were observed. The catheters remained patent for 6-12 months without reposition or repair. Plasma levels of 2 stress-labile hormones, PRL and cortisol, showed diurnal fluctuations comparable to those observed in untethered animals. The frequency of LH secretory episodes was determined by measuring bioactive LH in blood samples collected at 10-min intervals in the follicular phase and at 15-min intervals in the luteal phase of the menstrual cycle. In 10 trials during the follicular phase, we estimated that an average of between 14 and 15 LH pulses occurred every 12 h. The interpulse interval ranged between 20-80 min and averaged 50 min. No change in pulse frequency was observed across the follicular phase. The number of LH pulses decreased after ovulation, and by the end of the luteal phase, the interpulse interval was 4-6 h. One example during the preovulatory LH surge revealed the high frequency, high amplitude nature of LH secretion at that time. Our experience indicates that tethered animals with cardiac catheters show no hormonal indications of stress and represent the best available model for studies requiring frequent and prolonged access to the vascular system. Our data suggest that peripheral LH fluctuations in rhesus monkeys, as in other mammals, are pulsatile, and the frequency of these pulsatile episodes changes with different phases of the menstrual cycle, presumedly in response to varying stimuli to the pituitary from the brain.

Synthesis of two conformationally constrained analogues of the minor tobacco alkaloid anabasine.

The anabasine analogues spiro[4-azaindan-1,2'-piperidine] (7) and spiro[6-azaindan-1,2'-piperidine] (8) have been prepared. A series of palladium-catalyzed reactions, where an intramolecular cyclization constituted a key reaction, were utilized for the preparation of the two target compounds.

Atypical pyramidal cells in epileptic human cortex: CFLS and 3-D reconstructions.

Epileptic temporal cortices, removed from 3 patients with intractable partial epilepsy (IPE) during neurosurgery, were studied. Pyramidal neurons (40-50 per slice) in laminae III, V and white matter, were injected with lucifer yellow. Samples were examined in a confocal laser scanning microscope (Biorad 600) and individual cells scanned at 0.1-1 microns incremental levels. 2-D maximal linear projection was used for overview. Frames (50-60) of scanned neurons were transformed into 3-D volumes, using VoxelView software on a Silicone Graphics workstation and rotated. All samples contained neurons with duplicated apical dendrites, additional basal dendrites or were misplaced in a horizontal position in the white matter. The relation between these preliminary observations and the disease is discussed.

Amino acids in the dorsal lateral geniculate nucleus of the cat--collection in vivo.

A dialysis sampling probe was used to collect amino acids from the dorsal lateral geniculate nucleus (LGN) in vivo. The sampling probe was equipped with an electrode to allow local stimulation and recording of nerve activity. The amino acids in the dialysates were determined fluorimetrically by precolumn derivation and hplc-separation. Local electrical stimulation of the LGN caused a multifold increase in glutamate, aspartate and GABA levels. Smaller changes were observed for taurine, alanine and glycine. The results indicate that the dialysis sampling probe is rather atraumatic and can be used to detect stimulation-induced changes in extracellular amino acid concentrations.

A potential screening technique for neurotransmitters in the CNS: model studies in the cat spinal cord.

This paper describes a potential screening technique for neurotransmitters in the CNS. The method uses the injection of small volumes of high specific activity radioactive transmitter precursor substances into regions of physiologically identified neuronal cell bodies, and the later identification of the substances transported down axons to target tissues. Experiments were performed in motoneurons in the cat spinal cords to test the feasibility of method. Tritiated choline, glutamate, tyramine and tryptophan were pressure-injected into the ventral horn using glass micropipettes that were adapted to allow similtaneous physiological recording and injection. Only tritiated acetylcholine, two unidentified choline metabolites and a small amount of choline were found in the motor axons. The acetylcholine migrated at a rate of greater than 24mm/day and the movement was blocked by colchicine. The spread of isotope from the injection site was measured by a direct chemical method and by autoradiography, and was found that isotope spread1-2 mm from the injection site. One unexpected finding in the autoradiographs was that the motoneurons were selectively labelled following choline injections.

Electrical stimulation. A physiologic approach to the treatment of urinary incontinence.

Appropriate management of patients with urinary incontinence requires access to a variety of methods. Electrical stimulation, although so far proportionally small in the armamentarium of methods, is founded on physiologic principles and has the advantage of being curative without significant side effects.