Testicular cancer: a longitudinal pilot study on stress response symptoms and quality of life in couples before and after chemotherapy

Goals of work: The current study was designed to longitudinally examine stress response symptoms (SRS) and quality of life (QoL) in couples confronted with disseminated testicular cancer. The objectives were to examine couples' patterns of adjustment over time and possible differences in adjustment between the patient and his partner.Materials and methods: Couples completed the Impact of Event Scale and the QoL subscales physical functioning, social functioning, and mental health of the RAND-36 before chemotherapy (T1), after completion of chemotherapy (T2), and 1 year later (T3). Results: Before chemotherapy 26% of the patients and 50% of partners reported clinically elevated levels of SRS. Patients reported lower physical and social functioning at T2 compared to T1 and T3. Partners reported an improvement in social functioning over the year and no changes in physical functioning or mental health. No relationships between patients and partners' functioning were found. One year after diagnosis, QoL of patients and partners was similar to that of reference groups, and patients even reported better physical functioning than the reference group. SRS of patients and partners were negatively related at T1, and patients and partners' social functioning were positively related at T2. Conclusions: According to stress response levels, the period before the start of chemotherapy was most stressful for couples. Adjustment patterns differ between testicular cancer patients and their partners with patients reporting lowered QoL after completion of chemotherapy. QoL of couples returned to normal levels 1 year after diagnosis. The effect of disseminated testicular cancer on the QoL of patients and their partners seems to be temporary. A minority may need clinical attention for severe SRS

Feasibility of brief psychological distress screening by a community-based telephone helpline for cancer patients and carers

Background Up to one-third of people affected by cancer experience ongoing psychological distress and would benefit from screening followed by an appropriate level of psychological intervention. This rarely occurs in routine clinical practice due to barriers such as lack of time and experience. This study investigated the feasibility of community-based telephone helpline operators screening callers affected by cancer for their level of distress using a brief screening tool (Distress Thermometer), and triaging to the appropriate level of care using a tiered model. Methods Consecutive cancer patients and carers who contacted the helpline from September-December 2006 (n = 341) were invited to participate. Routine screening and triage was conducted by helpline operators at this time. Additional socio-demographic and psychosocial adjustment data were collected by telephone interview by research staff following the initial call. Results The Distress Thermometer had good overall accuracy in detecting general psychosocial morbidity (Hospital Anxiety and Depression Scale cut-off score ≥ 15) for cancer patients (AUC = 0.73) and carers (AUC = 0.70). We found 73% of participants met the Distress Thermometer cut-off for distress caseness according to the Hospital Anxiety and Depression Scale (a score ≥ 4), and optimal sensitivity (83%, 77%) and specificity (51%, 48%) were obtained with cut-offs of ≥ 4 and ≥ 6 in the patient and carer groups respectively. Distress was significantly associated with the Hospital Anxiety and Depression Scale scores (total, as well as anxiety and depression subscales) and level of care in cancer patients, as well as with the Hospital Anxiety and Depression Scale anxiety subscale for carers. There was a trend for more highly distressed callers to be triaged to more intensive care, with patients with distress scores ≥ 4 more likely to receive extended or specialist care. Conclusions Our data suggest that it was feasible for community-based cancer helpline operators to screen callers for distress using a brief screening tool, the Distress Thermometer, and to triage callers to an appropriate level of care using a tiered model. The Distress Thermometer is a rapid and non-invasive alternative to longer psychometric instruments, and may provide part of the solution in ensuring distressed patients and carers affected by cancer are identified and supported appropriately

Screening for psychological distress in patients with lung cancer: results of a clinical audit evaluating the use of the patient Distress Thermometer

Patients with lung cancer frequently suffer psychological distress and guidelines in the United Kingdom recommend screening of all cancer patients for this problem. The audit investigated use of the Distress Thermometer in terms of staff adherence to locally developed guidelines, patient willingness to use the tool, its impact on referral rates to clinical psychology services and concordance between the tool and the clinical assessment. Use of the Distress Thermometer was audited over a 3-month period in one lung cancer outpatient clinic. Referrals to clinical psychology services in response to clearly delineated referral indicators were assessed. Patient-reported outcomes were compared with practitioner assessment of need during clinical consultations to see whether the tool was measuring distress effectively. Thirty three of 34 patients used the Distress Thermometer during the audit period. Ten reported distress levels above 4 in the emotional or family problems domains. On ten occasions, the clinical interview identified problems not elicited by the Distress Thermometer. Guidelines were adhered to by staff, and patients were offered information about local support services and referral to clinical psychology services where indicated. Whilst all patients were happy to receive written information about further sources of support, none wanted to be referred to psychological services at that time. The Distress Thermometer is acceptable to patients with lung cancer in outpatient settings but it did not increase referrals for psychological support. Staff found it to be a useful tool in opening up communication about patient issues although it should not replace a comprehensive clinical interview

Evolutionary Convergence on Highly-Conserved 3′ Intron Structures in Intron-Poor Eukaryotes and Insights into the Ancestral Eukaryotic Genome

The presence of spliceosomal introns in eukaryotes raises a range of questions about genomic evolution. Along with the fundamental mysteries of introns' initial proliferation and persistence, the evolutionary forces acting on intron sequences remain largely mysterious. Intron number varies across species from a few introns per genome to several introns per gene, and the elements of intron sequences directly implicated in splicing vary from degenerate to strict consensus motifs. We report a 50-species comparative genomic study of intron sequences across most eukaryotic groups. We find two broad and striking patterns. First, we find that some highly intron-poor lineages have undergone evolutionary convergence to strong 3′ consensus intron structures. This finding holds for both branch point sequence and distance between the branch point and the 3′ splice site. Interestingly, this difference appears to exist within the genomes of green alga of the genus Ostreococcus, which exhibit highly constrained intron sequences through most of the intron-poor genome, but not in one much more intron-dense genomic region. Second, we find evidence that ancestral genomes contained highly variable branch point sequences, similar to more complex modern intron-rich eukaryotic lineages. In addition, ancestral structures are likely to have included polyT tails similar to those in metazoans and plants, which we found in a variety of protist lineages. Intriguingly, intron structure evolution appears to be quite different across lineages experiencing different types of genome reduction: whereas lineages with very few introns tend towards highly regular intronic sequences, lineages with very short introns tend towards highly degenerate sequences. Together, these results attest to the complex nature of ancestral eukaryotic splicing, the qualitatively different evolutionary forces acting on intron structures across modern lineages, and the impressive evolutionary malleability of eukaryotic gene structures

Inflammatory Genital Infections Mitigate a Severe Genetic Bottleneck in Heterosexual Transmission of Subtype A and C HIV-1

The HIV-1 epidemic in sub-Saharan Africa is driven largely by heterosexual transmission of non-subtype B viruses, of which subtypes C and A are predominant. Previous studies of subtype B and subtype C transmission pairs have suggested that a single variant from the chronically infected partner can establish infection in their newly infected partner. However, in subtype A infected individuals from a sex worker cohort and subtype B individuals from STD clinics, infection was frequently established by multiple variants. This study examined over 1750 single-genome amplified viral sequences derived from epidemiologically linked subtype C and subtype A transmission pairs very early after infection. In 90% (18/20) of the pairs, HIV-1 infection is initiated by a single viral variant that is derived from the quasispecies of the transmitting partner. In addition, the virus initiating infection in individuals who were infected by someone other than their spouse was characterized to determine if genital infections mitigated the severe genetic bottleneck observed in a majority of epidemiologically linked heterosexual HIV-1 transmission events. In nearly 50% (3/7) of individuals infected by someone other than their spouse, multiple genetic variants from a single individual established infection. A statistically significant association was observed between infection by multiple genetic variants and an inflammatory genital infection in the newly infected individual. Thus, in the vast majority of HIV-1 transmission events in cohabiting heterosexual couples, a single genetic variant establishes infection. Nevertheless, this severe genetic bottleneck can be mitigated by the presence of inflammatory genital infections in the at risk partner, suggesting that this restriction on genetic diversity is imposed in large part by the mucosal barrier

Co-regulation of a large and rapidly evolving repertoire of odorant receptor genes

The olfactory system meets niche- and species-specific demands by an accelerated evolution of its odorant receptor repertoires. In this review, we describe evolutionary processes that have shaped olfactory and vomeronasal receptor gene families in vertebrate genomes. We emphasize three important periods in the evolution of the olfactory system evident by comparative genomics: the adaptation to land in amphibian ancestors, the decline of olfaction in primates, and the delineation of putative pheromone receptors concurrent with rodent speciation. The rapid evolution of odorant receptor genes, the sheer size of the repertoire, as well as their wide distribution in the genome, presents a developmental challenge: how are these ever-changing odorant receptor repertoires coordinated within the olfactory system? A central organizing principle in olfaction is the specialization of sensory neurons resulting from each sensory neuron expressing only ~one odorant receptor allele. In this review, we also discuss this mutually exclusive expression of odorant receptor genes. We have considered several models to account for co-regulation of odorant receptor repertoires, as well as discussed a new hypothesis that invokes important epigenetic properties of the system

An adaptive radiation model for the origin of new gene functions

The evolution of new gene functions is one of the keys to evolutionary innovation. Most novel functions result from gene duplication followed by divergence. However, the models hitherto proposed to account for this process are not fully satisfactory. The classic model of neofunctionalization holds that the two paralogous gene copies resulting from a duplication are functionally redundant, such that one of them can evolve under no functional constraints and occasionally acquire a new function. This model lacks a convincing mechanism for the new gene copies to increase in frequency in the population and survive the mutational load expected to accumulate under neutrality, before the acquisition of the rare beneficial mutations that would confer new functionality. The subfunctionalization model has been proposed as an alternative way to generate genes with altered functions. This model also assumes that new paralogous gene copies are functionally redundant and therefore neutral, but it predicts that relaxed selection will affect both gene copies such that some of the capabilities of the parent gene will disappear in one of the copies and be retained in the other. Thus, the functions originally present in a single gene will be partitioned between the two descendant copies. However, although this model can explain increases in gene number, it does not really address the main evolutionary question, which is the development of new biochemical capabilities. Recently, a new concept has been introduced into the gene evolution literature which is most likely to help solve this dilemma. The key point is to allow for a period of natural selection for the duplication per se, before new function evolves, rather than considering gene duplication to be neutral as in the previous models. Here, I suggest a new model that draws on the advantage of postulating selection for gene duplication, and proposes that bursts of adaptive gene amplification in response to specific selection pressures provide the raw material for the evolution of new function

Structural Insights into Rotavirus Entry.

To initiate infection, non-enveloped viruses must recognize a target cell and penetrate the cell membrane by pore formation or membrane lysis. Rotaviruses are non-enveloped dsRNA viruses that infect the mature intestinal epithelium. They are major etiologic agents of diarrheal disease in human infants, as well as in young individuals of various avian and mammalian species. Rotavirus entry into the cell is a complex multistep process initiated by the interaction of the tip of the viral spike with glycan ligands at the cell surface, and driven by conformational changes of the proteins present in the outer protein capsid, the viral machinery for entry. This review feeds on the abundant structural information produced for rotavirus during the past 30 years and focuses on the structure and the dynamics of the rotavirus entry machinery. We survey the current models for rotavirus entry into cells.S