What's new in travellers' diarrhoea: updates on epidemiology, diagnostics, treatment and long-term consequences.

BACKGROUND: Travellers' diarrhoea (TD) is the most common clinical syndrome affecting travellers. This narrative review summarizes key discoveries reported in the last two years related to TD and suggests areas for future research. METHODS: A PubMed literature search was conducted for novel data in TD research published between 12 January 2018 and 12 January 2020. Inclusion was based on contribution to epidemiology, aetiology, diagnostics, management and long-term consequences and relevance to public health, discovery and clinical practice. RESULTS: The initial literature search yielded 118 articles. We retrieved 72 and reviewed 31 articles for inclusion. The findings support our understanding that TD incidence varies by traveller group and environment with students and military-travel remaining moderately high risk, and control of food and water in mass gathering events remain an important goal. The growth of culture-independent testing has led to a continued detection of previously known pathogens, but also an increased detection frequency of norovirus. Another consequence is the increase in multi-pathogen infections, which require consideration of clinical, epidemiological and diagnostic data. Fluoroquinolone resistant rates continue to rise. New data on non-absorbable antibiotics continue to emerge, offering a potential alternative to current recommendations (azithromycin and fluoroquinolones), but are not recommended for febrile diarrhoea or dysentery or regions/itineraries where invasive pathogens are likely to cause illness. Recent studies investigated the interaction of the microbiome in TD prevention and consequences, and while discriminating features were identified, much uncertainty remains. The prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) acquisition and carriage is increasing. Finally, continued research documents the post-infectious consequences, whereas mechanisms of reactive arthritis and post-infectious IBS necessitate further investigation. CONCLUSIONS: Globally, TD remains an important travel health issue and advances in our understanding continue. More research is needed to mitigate risk factors where possible and develop risk-based management strategies to reduce antibiotic usage and its attendant consequences.

Identification of the in vivo promoters of bacteriophages S13 and phi X174 and measurement of their relative activities.

Regions of bacteriophages phi X174 and S13 that contain putative promoter sequences were amplified by the polymerase chain reaction (PCR) and cloned into the reporter vector pKO-1. Assays of galactokinase activity revealed in vivo promoter activity in those constructs containing the promoter sequences with transcription initiation (+1) sites at nucleotide positions 45, 982, 1823, and 5211. These were identical in location to sequences with in vitro promoter activity and to the three known promoters PA, PB, and PD. P5211 is the location of a new, fourth, promoter. A site with a +1 position at nucleotide 4876, previously shown to initiate RNA synthesis in an in vitro run-off transcription assay, had no in vivo promoter activity. To investigate whether flanking sequences had effects on promoter activity, restriction fragments of phi X174 and S13 that encompass the in vivo promoters were cloned into the reporter vector pKO-1. The PA and P5211 promoter constructs showed dramatic effects with increases in activity of up to 7 times that shown with the PCR-generated promoter constructs. The phi X174 PB promoter construct had a 50% decrease in activity compared with the PCR-generated PB clone. While the data showed that in most instances promoter activity is affected by the flanking sequences in which the promoter is embedded, no general pattern correlating flanking sequences and promoter activity could be discerned. Additional evidence that the promoter sequence regions were active in vivo promoters was obtained by S1 nuclease mapping experiments. Initiation of RNA synthesis was shown at positions 45, 982, and 5211.

Mapping the initiation sites of in vitro transcripts of bacteriophage S13.

Analysis of in vitro run-off transcripts synthesized by Escherichia coli RNA polymerase holoenzyme on linearized bacteriophage S13 DNA templates revealed five major transcription initiation sites. The sites, located at positions 45, 982, 1823 (1827), 4876 and 5211, are each within the boundaries of promoters or putative promoters previously mapped by footprinting and RNA polymerase binding analyses. They correspond to initiations at promoters upstream of the A, B, and D genes, and at a medium-affinity and a high-affinity RNA polymerase binding site P5211, respectively. Sequence analysis of the 5'-ends of two transcripts confirmed their initiation with pppA at nt 982 and nt 5211, the B gene and high-affinity binding site P5211, respectively. Some of the transcripts initiated at nt 4876 and nt 5211 terminated at nt 64, providing direct evidence of the functionality of a p-independent termination site at nt 64.

Mapping of RNA polymerase binding sites in the H/A gene region of bacteriophage S13 by footprinting and exonuclease III analysis.

The H/A gene region of the bacteriophage S13 genome (map positions 4597 to 289) was analyzed for Escherichia coli RNA polymerase-binding sites by combined DNase I footprinting, exonuclease III analysis and DNA sequencing. Two high-affinity binding sites were identified, one corresponding to the A gene promoter at position 5384 to 56, overlapping the H/A intergenic region at position 1 to 63, the other at position 5171 to 5230, at the 3'-end of the H gene. A medium-affinity RNA polymerase binding site was mapped at position 4810 to 4850 in the middle of the H gene upstream of a low-affinity site at position 5280 to 5330. The studies complete footprinting analyses of the S13 genome from position 4597 to 2198 and in combination with previous studies on transcription provide definitive evidence on the position of the A gene promoter in S13 and the closely related phage psi X174.

Clinical significance of inpatient family intervention: conclusions from a clinical trial.

OBJECTIVE: To test whether the statistically significant results of a randomized clinical trial of an inpatient family intervention were clinically significant for hospital practice, the authors reanalyzed outcome data using a measure of clinical significance based on the extent to which patients had recovered during the course of the intervention. METHODS: A total of 169 hospitalized subjects and their families were randomly assigned to a psychoeducational inpatient family intervention or to a comparison group. Patient and family outcome measures were assessed at admission, discharge, and six and 18 months after admission. Analyses of statistically significant differences in outcome suggested that inpatient family intervention was effective for certain patient subgroups identified by gender and diagnosis. Global Assessment Scale scores two or more standard deviations above the pretreatment (admission) mean were used as indicators for clinically significant improvement. RESULTS: The reanalysis confirmed that inpatient family intervention was associated with clinically significant improvement at discharge, especially for female patients and patients with chronic schizophrenia and bipolar disorder. These effects were maintained six months after admission before attenuating at 18 months. CONCLUSIONS: Inpatient family intervention results in clinically meaningful outcomes for certain subgroups of patients and their families.

Conformation of magainin-2 and related peptides in aqueous solution and membrane environments probed by Fourier transform infrared spectroscopy.

The conformational properties of the magainin family of antimicrobial peptides in aqueous solution and in model membranes have been probed by Fourier transform infrared spectroscopy. The magainins were found to be structureless in aqueous solution at neutral pD, confirming other studies by Raman and circular dichroism spectroscopy. Increasing the pD to 10 induced the formation of predominantly alpha-helical secondary structures, with some beta-sheet. In the presence of negatively charged liposomes (dimyristoylphosphatidylglycerol), the peptides folded into alpha-helical secondary structures with some beta-sheet structure evident. On the other hand, in the presence of zwitterionic phospholipids (dimyristoylphosphatidylcholine), the spectra were identical to those in aqueous solution. For some magainins, the interaction with charged liposomes was modulated by the presence of cholesterol; cholesterol was found to promote the formation of beta-sheet structures, as evidenced by the appearance of amide I bands at 1614 and 1637 cm-1. Differences in structure were observed between the amidated and nonamidated forms of some peptides. From the data, a mechanism of antimicrobial action of the magainin family of peptides is proposed.

Antimicrobial peptides of frog skin.

A mechanism of action for frog skin antimicrobial peptides has been proposed, based on the amphipathic nature of the peptides when they contact bacterial surfaces. This results in anion channel formation and penetration of the membrane which allows efflux of OH- and uncoupling of respiration in the bacteria. The question of occurrence of human antimicrobial peptides analogous to those in frogs has not been answered but early studies indicate that Erspamer's prediction is correct.

Observation and theory in psychoanalysis: the self psychology of Heinz Kohut.

The development of self psychology by Heinz Kohut illustrates the influence of observational method on theory formation in psychoanalysis. In 1959 Kohut began to emphasize empathy and introspection over the traditional combination of free association and evenly suspended attention. This became an important part of a process of revision in psychoanalytic theory which culminated in self psychology. This paper demonstrates how and why that particular change in observational method influenced that particular revision of theory.

A randomized clinical trial of inpatient family intervention: VI. Mediating variables and outcome.

In a randomized clinical trial of Inpatient Family Intervention (IFI) for 169 inpatients with schizophrenia, affective disorder, and a residual group of other diagnoses, results suggested significant effects favoring IFI for patients and their families. The treatment effects were limited to females and to two diagnostic groups: chronic schizophrenia patients and the bipolar subgroup of affective disorders.

A randomized clinical trial of inpatient family intervention. IV. Followup results for subjects with schizophrenia.

This is the last of a series of four papers, here focussing on schizophrenia, which report followup data up to 18 months from a randomized clinical trial of a psychoeducational family intervention (IFI), which was added to medication and limited to the inpatient phase of treatment, after which post-hospital care was not controlled. Our data suggested that patients with poor prehospital functioning (i.e., the chronic patients) may benefit from inpatient family intervention, but this therapeutic effect appears to be limited to females and does not appear until 18 months postadmission. Families of patients with schizophrenia also show benefit from having received IFI, the effect is seen earlier than with the patients, and is associated with achieving the goals of IFI. The results in the IFI group could not be accounted for by improved post-hospital medication compliance, but they may be related to this group's greater tendency to obtain further family treatment after discharge.

Psychoanalytic observation.

The recent focus on empathy as the essential activity in psychoanalytic data gathering has underemphasized the complexity of psychoanalytic observation and has failed to identify what truly makes it unique among modes of psychological investigation. It is a process that includes introspection and empathy. However, it also includes the analyst's observation of the patient's behavior, and particularly verbal behavior, in a way that is not necessarily empathic. The psychoanalytic use of introspection and behavioral observation together, as they are modified by the analysand's free association and the analyst's evenly hovering attention, provides a unique method of data gathering. The transient, mutually related regressions of analyst and analysand which partly constitute the analyzing instrument modify the field of observation available to both, providing better access to derivatives of the analysand's unconscious mental functioning. This more complex concept of psychoanalytic observation, as opposed to that in which empathy is predominant, has important implications for psychoanalytic training, clinical work, and theory.

Gender and schizophrenia outcome: a clinical trial of an inpatient family intervention.

Several studies document sex differences in premorbid and intermorbid role functioning, showing less functional deficit among females. The specific nature of sex differences in role functioning is still poorly understood. The purpose of the present study was to investigate sex differences in symptomatology and role functioning in a sample of 92 inpatients hospitalized for an episode of DSM-III-diagnosed schizophrenic disorder. Patients were randomized at hospital admission to either of two treatment conditions: (1) multimodal hospital treatment with the addition of an inpatient family intervention (IFI) or (2) multimodal hospital treatment without IFI. Results indicated (1) sex differences in levels of substance abuse and antisocial behavior (worse for males both at admission and followup)--dimensions of psychopathology unrelated to the core features of schizophrenia; (2) superior family and occupational functioning in females at followup; and (3) superior clinical response of females to IFI. Data on family response to IFI suggest some ameliorative effects of IFI on critical family attitudes toward female patients as well as greater family compliance with IFI treatment among the families of females. Sex differences in intermorbid family and occupational functioning and response to a family-based psychosocial intervention are discussed in light of data on rejecting family attitudes toward the patient and sex differences in symptomatology. The possible influence of sex-differentiated social role demands on response to IFI is also discussed.

A randomized clinical trial of inpatient family intervention. V. Results for affective disorders.

This paper reports the results at follow-up of a randomized clinical trial of combining family intervention with drug treatment during hospitalization for patients with affective disorder. The results suggest that female bipolar patients and their families benefited from family intervention, whereas unipolar patients and families did not. Patient outcome was positively correlated with the achievement of the goals of family intervention.

A simplified procedure for cDNA and genomic library construction using nonpalindromic oligonucleotide adaptors.

The properties and characteristics of oligonucleotide adaptors for use in a simplified procedure for the construction of cDNA and genomic DNA libraries are described. The adaptors are suitable for joining to blunt ended cDNA or sheared genomic DNA, and then to the cohesive ends of restriction sites in vectors. Each adaptor consists of two oligonucleotides with complementary but nonpalindromic sequences that include an internal restriction site, a 5' phosphorylated blunt end, and an overlapping or staggered 5' hydroxylated end corresponding to a restriction endonuclease site in a vector of choice. Ligation of the blunt end to high molecular weight target DNA proceeds efficiently and there is no tandem concatenation of the adaptor. Insertion into the appropriate vector only requires ligation of the cohesive ends. There is no requirement for methylation, restriction enzyme cleavage, G-C tailing, or denaturation after ligation of the adaptor to the target DNA, all characteristics of other procedures.

A randomized clinical trial of inpatient family intervention, III: Effects at 6-month and 18-month follow-ups.

This paper focuses on the follow-up results of a randomized clinical trial of inpatient family intervention (IFI) that emphasized psychoeducation. Results for the sample of 169 psychiatric patients suggested that adding family treatment to standard hospital treatment was effective; however, the statistical interactions indicated that this therapeutic effect was restricted to female patients with schizophrenia or major affective disorder. The effect of family treatment on male patients with these diagnoses was minimal or slightly negative. In a group of patients with other diagnoses, the Treatment by Sex effect was reversed: male patients did better with the family treatment.

Inpatient family intervention: a randomized clinical trial. II. Results at hospital discharge.

Although family intervention is practiced in most psychiatric hospitals, to our knowledge, no adequately controlled studies of its efficacy exist. This study was designed to answer, in part, the question of the relative efficacy of hospitalization with family intervention as compared with hospitalization without family intervention for patients (1) with major psychiatric disorders, (2) in need of hospital treatment, and (3) for whom both treatments are judged clinically feasible. This article compares treatment results at the time of hospital discharge for 169 patients randomly assigned to the inpatient Family Intervention or comparison conditions. Inpatient Family Intervention had greater efficacy than the comparison treatment, mostly attributable to its effect on female patients, especially those patients (and their families) with affective disorder.

Organization of repetitive DNAs in the guinea pig genome.

Investigation of restriction enzyme families observed in Bam HI and Eco RI digest of guinea pig DNA has led to the demonstration of a 4.0 kb cryptic satellite called MRICp which has 6300 copies and comprises 1% of the total genome. MRICp has been shown to encompass the Eco RI 4.0 kb family, the Bam HI 3.4 kb family and the Bam HI 3.7 kb family. The 1.5 kb Eco RI family is part of an L1 LINE that is present in the guinea pig and in other rodentia. It is part of a larger LINE, probably 6.5 to 7 kb in size, and some copies are embedded in satellite I DNA sequences.

Mapping the B and D gene promoters of bacteriophage S13 by footprinting and exonuclease III analysis.

The region of the bacteriophage S13 genome which contains the B, K, and C genes and most of the A, D, and E genes (map positions 627 to 2198) was analyzed for Escherichia coli RNA polymerase-binding sites by combined DNase I footprinting, exonuclease III analysis, and DNA sequencing. Two high-affinity binding sites that correspond to the B and D gene promoters were mapped at positions 936 to 995 and 1779 to 1848, respectively. Positions 936 to 995 are in gene A, preceding the B gene, and positions 1779 to 1848 are in gene C, just preceding the D gene. In addition, two lower-affinity binding sites were identified at positions 1527 to 1538 and 1705 to 1756 preceding the C and D genes, respectively. The footprinting studies described here, in combination with previous studies on transcription, provide definitive evidence on the position of the B and D gene promoters in S13 and the closely related phage phi X174.

Goal Attainment Scaling. Relevance and replicability in follow-up of inpatients.

First proposed by Kiresuk in 1968, Goal Attainment Scaling has been widely and enthusiastically accepted as an evaluation tool in service delivery and education. However, it has not been much used in controlled research, probably because its reliability and validity have been questioned by critics. The authors have used Goal Attainment Scaling as one of a number of outcome measures in a research project on the effect of family intervention on inpatients. In the course of doing so, they have developed guidelines for gathering information, constructing goal scales, selecting expected outcome levels, and categorizing subsequent outcome data. They believe that these guidelines have clinical integrity and that their use would improve the reliability of goal attainment scaling without detracting from its value as an individualized measure. With these modifications, Goal Attainment Scaling can be made more systematic and therefore more reliable without losing its intrinsic value as an individually targeted outcome measure.

Localization of Escherichia coli RNA polymerase-binding sites on bacteriophage S13 replicative form I DNA by protection of restriction enzyme cleavage sites.

Protection of restriction endonuclease cleavage sites by Escherichia coli RNA polymerase bound to the replicative form I of bacteriophage S13 DNA has been used to identify a number of regions of RNA polymerase binding. Digestion with HincII, AluI, HinfI, or HaeIII, under conditions optimized for "open" complex formation, revealed 12 regions of RNA polymerase binding. Based on differential salt sensitivities, five of the regions were classified as strong or tight binding sites. These were located before genes A (two sites), B, and D and at the 5' end of gene F. The seven regions which exhibited weaker binding were located at the 5' end of gene C (two sites), in the middle of gene D, just before and at the 3' end of gene F, at the 5' end of gene G, and in the middle of gene H. The sites before genes B and D coincide with sites previously identified as promoters in bacteriophage phi X174. One of the sites before gene A, that at nucleotides 5175-5211, represents a new putative promoter site in bacteriophage S13 and phi X174 located before the previously identified A gene promoter at nucleotides 10-45.