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Background: Every year, many thousands of travellers return to the United Kingdom (UK) from visits to other countries and some will become unwell due to infections acquired abroad. Many imported infections have similar clinical presentations, such as fever and myalgia, so diagnostic testing is an important tool to improve patient management and outcomes. The aim of this study was to examine the demographics, travel history, presenting symptoms and diagnostic outcomes of referrals to the UK's specialist diagnostic Rare & Imported Pathogens Laboratory (RIPL) for the period 2015-2020., Methods: Anonymised clinical and laboratory data were extracted from RIPL's Laboratory Information Management System and cleaned prior to descriptive analysis of the data. Travel history data were mapped to one of eight world regions, whereas symptom data were categorised into presenting syndromes. Diagnostic data were categorised as either positive, equivocal or negative., Results: During the period 2015-2020, RIPL received 73 951 samples from 53 432 patients suspected of having infections that are rare in the UK. The most common age group for unwell returning travellers was 30-39 years and the most commonly reported travel destination was Southern and SE Asia. Dengue virus was the most diagnosed infection overall, followed by chikungunya, Zika, leptospirosis and spotted fever group Rickettsia. Dengue virus was among the top three most frequent diagnoses for all world regions except Europe and represented 62.5% of all confirmed/probable diagnoses., Conclusions: None of the top five infections diagnosed by RIPL in travellers are vaccine-preventable, therefore understanding traveller demographics, destination-specific risk factors and encouraging preventative behaviours is the best available strategy to reduce the number of returning travellers who become infected. Prompt referral of acute samples with a detailed travel history, including purpose of travel and activities undertaken as well as dates and destinations can be a valuable tool in designing public health interventions and diagnostic algorithms., (© International Society of Travel Medicine 2023. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The estrogen-synthesizing enzyme aromatase is abundant at the synapse in the zebra finch hippocampus (HP), and its inhibition impairs spatial memory function. To more fully test the role of local estradiol (E2) synthesis in memory, the HP of adult male zebra finches was exposed to either control pellets or those containing the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD), ATD and E2, ATD and the G protein-coupled estrogen receptor (GPER) agonist G1, or the antagonist G15 alone. Birds were tested for spatial memory acquisition and performance, and HP levels of the postsynaptic protein PSD95 were measured. ATD-treated birds took longer to reach criterion than control birds, whereas acquisition in ATD+E2 and ATD+G1 birds was indistinguishable from control and ATD treatments. Interestingly, all G15 birds failed to acquire the task. Following a retention interval, ATD birds took the longest to reach the (formerly) baited cup and made the most mistakes. ATD+E2 animals displayed the lowest retention latencies and made fewer mistakes than ATD-treated birds, and ATD+G1 birds did not significantly differ from controls in retention latencies. The amount of PSD95 in the HP was lowest in ATD-treated animals compared with birds with silicone-only-implanted craniotomies, ATD+E2, and ATD+G1 birds, who did not differ in this expression. Thus, spatial memory acquisition and performance appear aromatase and E2 dependent, an effect more reliably revealed after consolidation and/or recall compared to acquisition. E2 may exert this effect via GPERs, resulting in an increase in PSD95 levels that may modify receptor activity or intracellular signaling pathways to increase synaptic strength., (Copyright © 2017 Endocrine Society.)

Recent studies have revealed the presence and regulation of aromatase at the vertebrate synapse, and identified a critical role played by presynaptic estradiol synthesis in the electrophysiological response to auditory and other social cues. However, if and how synaptic aromatization affects behavior remains to be directly tested. We have exploited 3 characteristics of the zebra finch hippocampus (HP) to test the role of synaptocrine estradiol provision on spatial memory function. Although the zebra finch HP contains abundant aromatase transcripts and enzyme activity, immunocytochemical studies reveal widespread pre- and postsynaptic, but sparse to undetectable somal, localization of this enzyme. Further, the superficial location of the avian HP makes possible the more exclusive manipulation of its neurochemical characteristics without perturbation of the neuropil and the resultant induction of astroglial aromatase. Last, as in other vertebrates, the HP is critical for spatial memory performance in this species. Here we report that local inhibition of hippocampal aromatization impairs spatial memory performance in an ecologically valid food-finding task. Local aromatase inhibition also resulted in lower levels of estradiol in the HP, but not in adjacent brain areas, and was achieved without the induction of astroglial aromatase. The observed decrement in acquisition and subsequent memory performance as a consequence of lowered aromatization was similar to that achieved by lesioning this locus. Thus, hippocampal aromatization, much of which is achieved at the synapse in this species, is critical for spatial memory performance.

A specific pathologic diagnosis is important in malignant lymphoma because the diverse disease subtypes require tailored approaches to clinical management. Reliance on small samples obtained with cutting needles has been advocated as a less invasive alternative to using larger, excised samples. Although published studies have demonstrated the safety and apparent sufficiency of this approach in informing clinical care, none have systematically determined the accuracy of pathologic lymphoma subtyping based on very small samples. We used a tissue microarray representing 67 cases of malignant lymphoma and 17 samples of nonneoplastic lymphoid tissue to model lymphoma diagnosis in small samples. Overall, 73.8% of the cases were diagnosed with a level of confidence deemed sufficient for directing clinical management; 85.9% of these diagnoses were accurate. Small cell lymphomas with highly distinctive immunophenotypes, including small lymphocytic, mantle cell, and T-lymphoblastic lymphoma, were recognized most consistently and accurately in the small samples. In contrast, follicular lymphoma and marginal zone lymphoma were especially difficult. Our results indicate that the reliability of lymphoma diagnoses based on small samples is heavily influenced by lymphoma subtype.

Enantiomeric separations of fluorescently labeled amino acids are studied by capillary electrophoresis (CE) under a novel variety of experimental conditions. Three different labels are evaluated using two different additives: cyclodextrins (beta- and gamma-) and a dual surfactant system of sodium dodecyl sulfate and sodium taurodeoxycholate. Fluorescein-5-isothiocyanate is the best label to use in this cyclodextrin-based system, and dansyl chloride is the best label to use in this dual surfactant system. Possible limitations for separation of the enantiomers using the mixed micelle system include the fact that there is little interaction of the solute with the surfactants, the negative charge of the solute is limiting the separation window of the system, and the amount of the chiral phase available for partitioning is limited. The separations using cyclodextrins as a chiral selector show that the label affects migration order of the enantiomers, and the cyclodextrins are very effective in separating numerous enantiomers. Overall, cyclodextrins are the better buffer additive for CE use, and the dual surfactant systems, including sodium taurodeoxycholate, offer future promise.

In order to assess hepatic glycogen stores in patients with noninsulin dependent diabetes mellitus (NIDDM) after a 3-day fast, the incremental glucose response to 1.0 mg iv glucagon (glucose area under the curve, glucoseAUC) was assessed in 19 obese diabetic subjects after an overnight (14 h) fast and again after a 3-day (64 h) fast. Results were compared to those of lean (n = 6) and obese (n = 15) nondiabetic subjects. During the fast, plasma glucose fell significantly in the lean (4.9 +/- 0.2 to 3.9 +/- 0.2 mmol/L), obese (5.1 +/- 0.1 to 4.2 +/- 0.2 mmol/L), and diabetic (14.7 +/- 0.7 to 10.3 +/- 1.0 mmol/L) subjects. However, in contrast to the fall in glucoseAUC observed in the lean (92.4 +/- 15.4 to 39.9 +/- 8.1 mmol min-1 L-1, P less than 0.02) and obese (64.4 +/- 11.1 to 48.4 +/- 9.4 mmol min-1 L-1) subjects, the glucoseAUC increased in diabetic subjects from 81.6 +/- 8.6 to 103.9 +/- 8.8 mmol min-1 L-1 during the fast, and was significantly greater than that of either the lean (P less than 0.001) or obese (P less than 0.001) nondiabetic subjects after the 64-h fast. Evidence that the glucose response to glucagon after a 64-h fast represents glycogenolysis and not gluconeogenesis was provided by studies in 10 additional subjects (5 obese nondiabetic subjects and 5 patients with NIDDM). Overall hepatic glucose output calculated from glucose kinetic data [( 3-3H]glucose) increased in diabetic and nondiabetic subjects during the first 30 min after glucagon administration and fell progressively thereafter. However, no increase in alanine gluconeogenesis (14C-alanine incorporation into glucose) was observed after glucagon administration in either subject group. The paradoxical accumulation of glycogen in the patients with NIDDM during the fast occurred despite basal rates of hepatic glucose output on the third day of the fast which were greater than those of obese nondiabetic subjects (9.0 +/- 1.2 vs. 5.6 +/- 0.5 mumol kg-1 min-1, P less than 0.05). A glycogen sparing action of increased gluconeogenesis is proposed as the explanation for the preservation of liver glycogen in patients with NIDDM.

The purpose of the present study was to compare the relative merits of cold acetone and buffered formalin as fixatives for the detection of carcinoembryonic antigen and keratin in permanently embedded tissues using a peroxidase-antiperoxidase (PAP) immunohistochemical procedure. The effect of treatment with the proteolytic enzyme pronase also was examined in the formalin-fixed tissues. Cold acetone was found to be superior to formalin for the preservation of CEA and keratin antigenic activities in a variety of benign and malignant tissues. Pronase treatment markedly increased the staining intensities of both antigens in formalin-fixed tissues. For many tissues, however, superior results were obtained using the cold acetone method, and this technic is recommended for the optimum retention of antigenic activity in permanently embedded tissues.

The uptake of androgens into the nuclei of caput epididymis, ventral prostate, seminal vesicle and testis was studied by recirculating physiological and pharmacological concentrations of [3H]testosterone in an artificial medium through the lower half (hemicorpus) of castrated or hypophysectomized rats. The accumulation of dihydrotestosterone in accessory sex organ nuclei was saturable, inhibited by perfusion of excess testosterone or cyproterone acetate, and associated with binding to 3S salt-extractable molecules. In castrated preparations the mean saturation levels (pmol/mg DNA) were different in the three organs: seminal vesicle, 2.8; ventral prostate, 1.8; caput epididymis, 0.9. The saturation level was significantly lower in ventral prostate of hypophysectomized rats (1.2) treated with testosterone to regenerate the accessory sex organs. Testosterone was the major nuclear androgen in the testes of mature hypophysectomized preparations perfused with testosterone. Although there was a large amount of nonspecific accumulation, testosterone binding to 3S molecules was shown by sucrose gradient centrifugation. Binding of dihydrotestosterone to 3S molecules in testicular nuclei was also demonstrated. The ratio of dihydrotestosterone to testosterone was different in immature and mature testicular nuclei and was altered by treatments known to affect testicular 5 alpha-reductase activity. The results suggest that in rat accessory sex organs and immature testis the major active androgen is dihydrotestosterone, whereas in mature testis it is testosterone. The shift in the predominant nuclear androgen in the testis from dihydrotestosterone to testosterone is most simply explained by the maturational change in 5 alpha-reductase activity.