Potential for using simulated altitude as a means of prehabilitation: a physiology study.

The current pandemic of surgical complications necessitates urgent and pragmatic innovation to reduce postoperative morbidity and mortality, which are associated with poor pre-operative fitness and anaemia. Exercise prehabilitation is a compelling strategy, but it has proven difficult to establish that it improves outcomes either in isolation or as part of a multimodal approach. Simulated altitude exposure improves performance in athletes and offers a novel potential means of improving cardiorespiratory and metabolic fitness and alleviating anaemia within the prehabilitation window. We aimed to provide an initial physiological foundation for 'altitude prehabilitation' by determining the physiological effects of one week of simulated altitude (FI O2 15%, equivalent to approximately 2438 m (8000 ft)) in older sedentary volunteers. The study used a randomised, double-blind, sham-controlled crossover design. Eight participants spent counterbalanced normoxic and hypoxic weeks in a residential hypoxia facility and underwent repeated cardiopulmonary exercise tests. Mean (SD) age of participants was 64 (7) y and they were unfit, with mean (SD) baseline anaerobic threshold 12 (2) ml.kg-1 .min-1 and mean (SD) peak V̇O2 15 (3) ml.kg-1 .min-1 . Hypoxia was mild (mean (SD) Sp O2 93 (2) %, p < 0.001) and well-tolerated. Despite some indication of greater peak exercise capacity following hypoxia, overall there was no effect of simulated altitude on anaerobic threshold or peak V̇O2 . However, hypoxia induced a substantial increase in mean (SD) haemoglobin of 1.5 (2.7) g.dl-1 (13% increase, p = 0.028). This study has established the concept and feasibility of 'altitude prehabilitation' and demonstrated specific potential for improving haematological fitness. Physiologically, there is value in exploring a possible role for simulated altitude in pre-operative optimisation.

Integration of spatial and single-cell transcriptomic data elucidates mouse organogenesis.

Molecular profiling of single cells has advanced our knowledge of the molecular basis of development. However, current approaches mostly rely on dissociating cells from tissues, thereby losing the crucial spatial context of regulatory processes. Here, we apply an image-based single-cell transcriptomics method, sequential fluorescence in situ hybridization (seqFISH), to detect mRNAs for 387 target genes in tissue sections of mouse embryos at the 8-12 somite stage. By integrating spatial context and multiplexed transcriptional measurements with two single-cell transcriptome atlases, we characterize cell types across the embryo and demonstrate that spatially resolved expression of genes not profiled by seqFISH can be imputed. We use this high-resolution spatial map to characterize fundamental steps in the patterning of the midbrain-hindbrain boundary (MHB) and the developing gut tube. We uncover axes of cell differentiation that are not apparent from single-cell RNA-sequencing (scRNA-seq) data, such as early dorsal-ventral separation of esophageal and tracheal progenitor populations in the gut tube. Our method provides an approach for studying cell fate decisions in complex tissues and development.

Preliminary images from an adaptive imaging system.

I-ImaS (Intelligent Imaging Sensors) is a European project aiming to produce real-time adaptive X-ray imaging systems using Monolithic Active Pixel Sensors (MAPS) to create images with maximum diagnostic information within given dose constraints. Initial systems concentrate on mammography and cephalography. In our system, the exposure in each image region is optimised and the beam intensity is a function of tissue thickness and attenuation, and also of local physical and statistical parameters in the image. Using a linear array of detectors, the system will perform on-line analysis of the image during the scan, followed by optimisation of the X-ray intensity to obtain the maximum diagnostic information from the region of interest while minimising exposure of diagnostically less important regions. This paper presents preliminary images obtained with a small area CMOS detector developed for this application. Wedge systems were used to modulate the beam intensity during breast and dental imaging using suitable X-ray spectra. The sensitive imaging area of the sensor is 512 x 32 pixels 32 x 32 microm(2) in size. The sensors' X-ray sensitivity was increased by coupling to a structured CsI(Tl) scintillator. In order to develop the I-ImaS prototype, the on-line data analysis and data acquisition control are based on custom-developed electronics using multiple FPGAs. Images of both breast tissues and jaw samples were acquired and different exposure optimisation algorithms applied. Results are very promising since the average dose has been reduced to around 60% of the dose delivered by conventional imaging systems without decrease in the visibility of details.

Correlation of energy dispersive diffraction signatures and microCT of small breast tissue samples with pathological analysis.

Identification of specific tissue types in conventional mammographic examinations is extremely limited. However, the use of x-ray diffraction effects during imaging has the potential to characterize the tissue types present due to the fact that each tissue type produces its own unique diffraction signature. Nevertheless, the analysis and categorization of these diffraction signatures by tissue type can be hampered by the inhomogeneous nature of breast tissue, leading to categorization errors where several types are present. This work aims to reduce sample categorization errors by combining spectral diffraction signature collection with sample imaging, giving more detailed data on the composition of each sample. Diffraction microCT was carried out on 19 unfixed breast tissue samples using an energy resolving translate-rotate CT system. High-resolution transmission microCT images were also recorded for comparison and sample composition analysis. Following imaging, the samples were subjected to histopathological analysis. Reconstructing on various momentum transfer regions allows different tissue types to be identified in the diffraction images. Results show a correlation between measured x-ray diffraction images and stained histopathological tissue sections. X-ray diffraction signatures generated from the measured data were categorized and analysed, with a t-test indicating that they have the potential for use in tissue type identification.

Identification of full-length and truncated forms of Ehk-3, a novel member of the Eph receptor tyrosine kinase family.

Factors that bind and activate receptor tyrosine kinases are known to play key roles during development and in the adult. The Eph-related receptors constitute the largest known family of receptor tyrosine kinases. Members of the Eph family exhibit intriguing patterns of expression in the embryo, implicating them in a variety of developmental processes, and their expression is often restricted to particular subpopulations of postmitotic neurons in the adult. We describe the identification and characterization of a novel member of the Eph receptor family, which we have termed Ehk-3 for Eph Homologous Kinase 3. Ehk-3 displays all the major structural features shared by other members of the Eph family, including a cysteine-rich region and tandem fibronectin type-III domains in its extracellular portion. Ehk-3 is expressed in two forms in a developmentally-regulated fashion: a conventional full-length version containing the intracellular tyrosine kinase domain, as well as a truncated form that lacks this domain. Both forms of Ehk-3 are quite restricted to the nervous system in the adult, but Ehk-3 is more widely expressed in the embryo, suggesting that Ehk-3 mediates different functions during development and in the adult.

Characterization study of an intensified complementary metal-oxide-semiconductor active pixel sensor.

An intensified CMOS active pixel sensor (APS) has been constructed for operation in low-light-level applications: a high-gain, fast-light decay image intensifier has been coupled via a fiber optic stud to a prototype "VANILLA" APS, developed by the UK based MI3 consortium. The sensor is capable of high frame rates and sparse readout. This paper presents a study of the performance parameters of the intensified VANILLA APS system over a range of image intensifier gain levels when uniformly illuminated with 520 nm green light. Mean-variance analysis shows the APS saturating around 3050 Digital Units (DU), with the maximum variance increasing with increasing image intensifier gain. The system's quantum efficiency varies in an exponential manner from 260 at an intensifier gain of 7.45 × 10(3) to 1.6 at a gain of 3.93 × 10(1). The usable dynamic range of the system is 60 dB for intensifier gains below 1.8 × 10(3), dropping to around 40 dB at high gains. The conclusion is that the system shows suitability for the desired application.

A national survey of intensive care follow-up clinics.

Intensive care follow-up clinics allow extended review of survivors of critical illness. However, the current provision of intensive care follow-up clinics in the UK is unknown. We performed a survey of intensive care follow-up clinic practice in the UK. A questionnaire was sent to 298 intensive care units in the UK to determine the number of follow-up clinics and details of current follow-up practice. Responses were received from 266 intensive care units, an 89% response rate. Eighty units (30%) ran a follow-up clinic. Only 47 (59%) of these clinics were funded. Of those intensive care units without a follow-up clinic, 158 (88%) cited 'financial constraints' as the reason. Over half of the follow-up clinics (44 clinics, 55%) were nurse-led, and the majority (56 clinics, 77%) only routinely review patients treated on the intensive care unit for 3 or 4 days or longer. Nearly half of the follow-up clinics (39 clinics, 49%) have pre-negotiated access to at least one other out-patient service.

Clinal variation and laboratory adaptation in the rainforest species Drosophila birchii for stress resistance, wing size, wing shape and development time.

Clinal variation has been described in many invertebrates including drosophilids but usually over broad geographical gradients. Here we describe clinal variation in the rainforest species Drosophila birchii from Queensland, Australia, and potential confounding effects of laboratory adaptation. Clinal variation was detected for starvation and development time, but not for size or resistance to temperature extremes. Starvation resistance was higher at southern locations. Wing shape components were not associated with latitude although they did differ among populations. Time in laboratory culture did not influence wing size or heat knockdown resistance, but increased starvation resistance and decreased recovery time following a cold shock. Laboratory culture also increased development time and altered wing shape. The results indicate that clinal patterns can be detected in Drosophila over a relatively narrow geographical area. Laboratory adaptation is unlikely to have confounded the detection of geographical patterns.

The organ distribution of F protein in the mouse.

F protein is of unknown function and found principally in the liver, with smaller amounts detectable by gel diffusion and immunostaining in kidney and brain. By taking advantage of a newly developed radioimmunoassay, capable of detecting down to 1 ng ml-1 of F protein, the organ distribution of this molecule in the mouse was re-examined. F protein was not confined to the previously known tissues and indeed was detected at different levels in every organ studied. The highest concentration (6-10 mg g-1 wet tissue) was found in the liver, but significant amounts (2-25 micrograms g-1) were also found in kidney, heart, and brain. Lower quantities were detectable in all other tissues studied. The presence of F protein in the thymus, and the lack of tolerance to this in bone marrow chimaeras between mice of different F protein types, places certain constraints on the amount and/or location of a protein required for tolerization.

The traditional healer/diviner as psychotherapist.

Appreciation of the apparent efficacy of the traditional healer/diviner in the alleviation of psychological disturbances led to an examination of his/her methods and training in comparison to those of the Western psychotherapist. Models of the themes, components and effects of psychotherapy can be seen to be applicable in both instances, although the functions and roles of healers and psychotherapists in their respective societies may differ. The implications of these analyses as regards the enhancement of the effects of therapeutic intervention are examined.

Errors in the diagnosis of schizophrenia in black and Indian patients.

The referral and/or final diagnoses of schizophrenia in 100 patients were examined. Discrepancies between these diagnoses were frequent and little evidence of a standardized approach to this diagnosis was revealed. Misinterpretation of cultural phenomena emerged as a further source of error. The critical nature of the interview and assessment situation, together with the need for standardized criteria and comprehensive understanding of cultural factors, is emphasized.

Female bladder problems - a case for psychotherapy? A case report.

The case of a 31-year-old woman suffering from repeated episodes of urinary retention is presented. Several surgical procedures had given her only temporary relief. When the patient presented with overt depression and anxiety she was assessed psychiatrically, and it was noted that the urinary retention coincided with episodes of domestic emotional distress. A behavioural treatment programme was initiated and a remission of the urological symptoms rapidly achieved. The importance of psychotherapeutic intervention in such cases is emphasized.

Sickness and medicine--an African paradigm.

The concepts of sickness employed in the practice of Western medicine and those held by the Nguni peoples in Africa are shown to be disparate. The approach of the so-called 'traditional healer' incorporates the world-view of the culture within which she works, and her ministrations are consonant with the prevailing beliefs of the community. It is therefore postulated that within this context the application of conventional Western therapeutic techniques can be inappropriate and consequently ineffective.

Priests before healers--an appraisal of the iSangoma or iSanusi in Nguni society.

The total role of the iSangoma or iSanusi within the Nguni culture in Africa is discussed. The importance of the religious and social functions and divinatory powers are emphasized in an endeavour to determined the bases for the therapeutic capacities associated with the so-called 'traditional healer'.

The genetic relationship between the human foetal acetylesterase ESA7 and the adult acetylesterase ESA5.

(1) There are very few clear examples among human enzymes of foetal isozymes which are the products of foetal specific gene loci. Earlier studies had pointed to the foetal brain esterase ESA7 as a probable example. (2) Detailed biochemical investigation of partially purified human adult brain ESA5 and the foetal esterase ESA7 has revealed a close resemblance in the biochemical properties of these two isozymes. In addition to similarities in substrate specificity and inhibition sensitivity the two esterases have the same molecular size (c. 57,000), are both relatively unstable at 37 degrees C and show decreased anodal electrophoretic mobility after storage at 20 degrees C. Furthermore there was suggestive evidence that ESA7 and ESA5 may be interconvertible. (3) A variant esterase isozyme pattern, which shows unusual features of both ESA7 and ESA5, was found in a survey of 120 foetal brains. This variant pattern is consistent with a monomeric structure for both esterases and points strongly to a common genetic determination.

Detection of a Yb3+ binding site in regenerated bacteriorhodopsin that is coordinated with the protein and phospholipid head groups.

Near infrared Yb3+ vibronic sideband spectroscopy was used to characterize specific lanthanide binding sites in bacteriorhodopsin (bR) and retinal free bacteriorhodopsin (bO). The VSB spectra for deionized bO regenerated with a ratio of 1:1 and 2:1 ion to bO are identical. Application of a two-dimensional anti-correlation technique suggests that only a single Yb3+ site is observed. The Yb3+ binding site in bO is observed to consist of PO2- groups and carboxylic acid groups, both of which are bound in a bidentate manner. An additional contribution most likely arising from a phenolic group is also observed. This implies that the ligands for the observed single binding site are the lipid head groups and amino acid residues. The vibronic sidebands of Yb3+ in deionized bR regenerated at a ratio of 2:1 ion to bR are essentially identical to those in bO. The other high-affinity binding site is thus either not evident or its fluorescence is quenched. A discussion is given on the difference in binding of Ca2+ (or Mg2+) and lanthanides in phospholipid membrane proteins.

Parasuicide in the Durban Indian community.

Biographical and psychiatric factors in 100 patients referred to a department of psychiatry after a suicide attempt were surveyed. One of the major precipitants of parasuicide in the present study, and found in all cases, was an interpersonal dispute; this involved extended family in 63 cases and marital or romantic relationships in 81.

Deculturation as a precipitant of parasuicide in an Asian group.

The Durban Indian community has been described as an acculturating or a deculturating community. The processes of acculturation and deculturation are seen to lead to a transitional state of values and norms which causes psychological stresses within the community. Deviation from accepted cultural norms and concomitant interpersonal disputes were major precipitating factors in parasuicidal acts in 54 of a sample of 100 patients, reflecting the stresses of the transitional state of the community. Culturally deviant precipitating factors in the parasuicidal act were more common in females, in the younger age group, in patients of the Christian religion, and in upper- and middle-class patients.

Angiopoietins 3 and 4: diverging gene counterparts in mice and humans.

The angiopoietins have recently joined the members of the vascular endothelial growth factor family as the only known growth factors largely specific for vascular endothelium. The angiopoietins include a naturally occurring agonist, angiopoietin-1, as well as a naturally occurring antagonist, angiopoietin-2, both of which act by means of the Tie2 receptor. We now report our attempts to use homology-based cloning approaches to identify new members of the angiopoietin family. These efforts have led to the identification of two new angiopoietins, angiopoietin-3 in mouse and angiopoietin-4 in human; we have also identified several more distantly related sequences that do not seem to be true angiopoietins, in that they do not bind to the Tie receptors. Although angiopoietin-3 and angiopoietin-4 are strikingly more structurally diverged from each other than are the mouse and human versions of angiopoietin-1 and angiopoietin-2, they appear to represent the mouse and human counterparts of the same gene locus, as revealed in our chromosomal localization studies of all of the angiopoietins in mouse and human. The structural divergence of angiopoietin-3 and angiopoietin-4 appears to underlie diverging functions of these counterparts. Angiopoietin-3 and angiopoietin-4 have very different distributions in their respective species, and angiopoietin-3 appears to act as an antagonist, whereas angiopoietin-4 appears to function as an agonist.