Age-related hearing loss (ARHL) is common and a known risk factor for social disengagement in later life. This study explored social functioning following a diagnosis of ARHL. Using a constructivist grounded theory approach we developed an interview schedule to advance a grounded theory from data collected from six older adults who used either hearing aids or cochlear implants. Interview questions concerned social functioning as well as focusing on their perspective of the impact of ARHL on cognitive functioning. We describe a grounded theory conceived as ‘Reconnecting to Others’. This theory posits that participants faced social challenges in relation to their ARHL, and resolved these challenges partly through the use of hearing aids and cochlear implantation. The theory also emphasises the importance of help from other hearing aid users for new users, and corroborates prior findings about strategies older adults with ARHL use to cope with their hearing impairment in various social situations. Once hearing aids and cochlear implants are used and adapted to with the help of peers, participants completed their journey by helping others who had received diagnoses of ARHL. Additionally, participants spoke of the pleasure of hearing again. Interestingly, no participant felt that their ARHL had impacted their cognitive functioning. Our theory provides a basis for explaining existing quantitative findings as well as creating new hypotheses for future testing.

Dietrich Bonhoeffer's pursuit of a sanctified life took a significant detour from the way in which he thought it would proceed. In seeking ‘good’ moral choices in the crucible of Nazi Germany, Bonhoeffer experienced a profound sense of what we now would recognise as moral injury, which proves to be a powerful and reflexive lens with which to examine his understanding of sanctification. Initially embracing pacifism as a fundamental pillar of Christian life, Bonhoeffer eventually became convinced that there are no pure or ‘right’ moral choices, only competing ‘wrong’ ones. He later wrote from prison that to be like Christ, and to come closer to holiness, was not to seek to avoid guilt, but to take on guilt for the sake of others. This recontextualisation of the idea of sanctification through the lens of Christ's substitutionary guilt suggests that for the responsible actor moral injury may be inevitable.

Mealtime interventions typically focus on institutionalised older adults, but we wanted to investigate whether they may also be effective among those living independently. Using a randomised controlled trial design, we assessed the effects of a novel mealtime intervention on self-efficacy, food enjoyment and energy intake. A total of 100 adults living alone aged over 60 years were randomised to the treatment or control conditions: all received a guidebook on nutrition and culinary skills. Treatment group participants received a weekly visit from a trained volunteer who prepared and shared a meal with them. Participants in the treatment group showed improvements relative to those in the control group at borderline significance (P=0·054) for self-efficacy and at significance for food enjoyment. Significant improvements were observed in female participants in the treatment but not in the control group in energy intake (although following corrections for multiple comparisons, only the effect on food enjoyment remained significant). These findings will inform the design of future complex interventions. For this type of intervention to be successful, more focus has to be placed on making interventions more personalised, potentially according to sex. Findings are important for nutritional sciences as they indicate that, in order to improve energy intake and food enjoyment among older adults, multimodal nutritional interventions including social components may be successful.

We report the clinical and laboratory findings of six Canadian patients with progressive myelopathy associated with HTLV-1 infection. The diagnosis was suspected on clinical grounds and supported by serological studies and positive gene amplification. Only five had emigrated from an area endemic for HTLV-1 infection. Tropical spastic paraparesis should be considered in all patients with myelopathy, even those without standard serological markers of HTLV-1 infection. The pathogenesis of this condition and the serological and molecular biological means by which this diagnosis can be made are reviewed.

We report the pathological and molecular biological findings of human T-cell lymphotropic virus type 1 (HTLV-1) infection of the spinal cord in a patient with a chronic progressive myelopathy. Light microscopy disclosed loss of myelin and axons, thickening of blood vessels and a lymphocytic cell infiltrate in the spinal cord especially at the cervical and thoracic levels. Electron microscopy confirmed the vascuolar appearance seen with light microscopy but virus particles were not observed. The HTLV-1 gag gene could be amplified (by polymerase chain reaction) from cervical spinal cord tissue while not from elsewhere in the neuroaxis. The presence of HTLV-1 geonomic material in spinal cord tissue has not been previously reported.

Background: There is ongoing debate about whether a decline in body mass represents a true risk factor for dementia, whether it is a phenotypic marker of incipient dementia, or perhaps a marker of another process that increases dementia risk. This study was designed to determine if changes in body mass index (BMI) in later life are associated with hazard of incident dementia over a follow-up period of up to eight years.

Methods: Method followed was a prospective cohort study of 4,181 men aged 65–84 years, resident in Perth, Australia. The exposure of interest was change in BMI measured between 1996–1998 and 2001–2004. The outcome was incident dementia, established using the Western Australia Data Linkage System until 2009. We used Cox regression models to establish crude and adjusted hazard of dementia for change in BMI.

Results: Compared with men with a stable BMI, those with a decrease in BMI >1 kg/m2 had a higher adjusted hazard of dementia (hazard ratio (HR) = 1.89, 95% CI = 1.32–2.70). The cumulative hazard of dementia over follow-up for changes in BMI was greatest for men with a decrease in BMI >1 kg/m2; this trend was apparent for men in all BMI categories (underweight, normal, overweight, obese). A reverse “J-shaped” association between BMI change and incident dementia was observed, with the lowest dementia rate being for men whose BMI remained stable.

Conclusions: Men who maintained a stable body mass had the lowest incidence of dementia. Further studies are needed to clarify causality and assess feasibility of interventional studies to preserve body mass in aging men.

Here we examine the patterns of connections between the zona incerta (ZI) of the thalamus and the major visual centers of the rat brain, namely the retina, dorsal lateral geniculate nucleus (LGd), superficial layers of the superior colliculus (SCs), and occipital cortex (Oc1). Injections of the tracers biotinylated dextran or cholera toxin subunit b were made into each of these centers, as well as ZI itself, by using stereotaxic coordinates. Rat brains were then aldehyde-fixed and processed using standard methods. We show that the retina, LGd, SCs, and Oc1 all have connections with ZI; moreover, that each of these connections make a very distinct territory or subsector within the most lateral ZI regions. This subsector of connectivity with the visual centers does not respect the well-defined cytoarchitectonic sectors of ZI, being made up of small zones in the dorsal, ventral, and caudal sectors. Often, a distinctive “horse-shoe” pattern is evident, particularly after retinal and Oc1 injections. Tracer injections into topographically distinct regions of the LGd, SCs, or Oc1 results in no shift in the spatial location of labelling within ZI; after each injection, labelling is always seen within the lateral edge of the nucleus. Labelled terminals and cells are seen after LGd and SCs injections, while only labelled terminals are seen after retinal and Oc1 injections. Although the precise function of this novel visual subsector is not known, these early findings suggest that ZI may be in a position to integrate visual information together with the other somatosensory, motor, and visceral information that it receives.

β-Lactamases are the major resistance mechanism to β-lactam antibiotics and pose a growing threat to public health. Recently, bacteria have become resistant to β-lactamase inhibitors, making this problem pressing. In an effort to overcome this resistance, non-β-lactam inhibitors of β-lactamases were investigated for complementarity to the structure of AmpC β-lactamase from Escherichia coli. This led to the discovery of an inhibitor, benzo(b)thiophene-2-boronic acid (BZBTH2B), which inhibited AmpC with a Ki of 27 nM. This inhibitor is chemically dissimilar to β-lactams, raising the question of what specific interactions are responsible for its activity. To answer this question, the X-ray crystallographic structure of BZBTH2B in complex with AmpC was determined to 2.25 Å resolution. The structure reveals several unexpected interactions. The inhibitor appears to complement the conserved, R1-amide binding region of AmpC, despite lacking an amide group. Interactions between one of the boronic acid oxygen atoms, Tyr150, and an ordered water molecule suggest a mechanism for acid/base catalysis and a direction for hydrolytic attack in the enzyme catalyzed reaction. To investigate how a non-β-lactam inhibitor would perform against resistant bacteria, BZBTH2B was tested in antimicrobial assays. BZBTH2B significantly potentiated the activity of a third-generation cephalosporin against AmpC-producing resistant bacteria. This inhibitor was unaffected by two common resistance mechanisms that often arise against β-lactams in conjunction with β-lactamases. Porin channel mutations did not decrease the efficacy of BZBTH2B against cells expressing AmpC. Also, this inhibitor did not induce expression of AmpC, a problem with many β-lactams. The structure of the BZBTH2B/AmpC complex provides a starting point for the structure-based elaboration of this class of non-β-lactam inhibitors.