Flight muscle and heart phenotypes in the high-flying ruddy shelduck.

Ruddy shelduck migrate from wintering grounds in lowland India and Myanmar to breeding grounds in central China and Mongolia, sustaining flight over the Himalayas, where oxygen availability is greatly reduced. We compared phenotypes of the pectoralis muscle and the ventricle of the heart from ruddy shelduck and common shelduck (a closely related low-altitude congener) that were raised in common conditions at sea level, predicting that oxidative capacity would be greater in ruddy shelduck to support high-altitude migration. Fibre-type composition of the pectoralis and the maximal activity of eight enzymes involved in mitochondrial energy metabolism in the pectoralis and heart, were compared between species. Few differences distinguished ruddy shelduck from common shelduck in the flight muscle, with the exception that ruddy shelduck had higher activities of complex II and higher ratios of complex IV (cytochrome c oxidase) and complex II when expressed relative to citrate synthase activity. There were no species differences in fibre-type composition, so these changes in enzyme activity may reflect an evolved modification in the functional properties of muscle mitochondria, potentially influencing mitochondrial respiratory capacity and/or oxygen affinity. Ruddy shelduck also had higher lactate dehydrogenase activity concurrent with lower pyruvate kinase and hexokinase activity in the left ventricle, which likely reflects an increased capacity for lactate oxidation by the heart. We conclude that changes in pathways of mitochondrial energy metabolism in the muscle and heart may contribute to the ability of ruddy shelduck to fly at high altitude.

Different strategies for convective O2 transport in high altitude birds: A graphical analysis.

For illustrative purposes, in this article we use "Johansen Plots" as a graphical way of simultaneously visualizing the inter-connected variables that compose the convective steps of the gas transport cascade. These plots are used to reflect on some of the physiological characteristics seen in five species of birds, four of which sojourn to, or are native to, high altitudes (the barnacle goose, bar-headed goose, Andean goose, speckled teal and ruddy duck). These species were chosen to emphasize the diversity of responses to hypoxia that can exist within a single family. This diversity likely arose for many possible reasons, including local adaptation to hypoxia, differences in flight or diving abilities, or as a result of other phylogenetically-based differences across waterfowl in physiology, behaviour, and/or life style.

Characterizing the influence of chronic hypobaric hypoxia on diaphragmatic myofilament contractile function and phosphorylation in high-altitude deer mice and low-altitude white-footed mice.

Deer mice, Peromyscusmaniculatus, live at high altitudes where limited O2 represents a challenge to maintaining oxygen delivery to tissues. Previous work has demonstrated that hypoxia acclimation of deer mice and low altitude white-footed mice (P. leucopus) increases the force generating capacity of the diaphragm. The mechanism behind this improved contractile function is not known. Within myocytes, the myofilament plays a critical role in setting the rate and level of force production, and its ability to generate force can change in response to changes in physiological conditions. In the current study, we examined how chronic hypobaric hypoxia exposure of deer mice and white-footed mice influences the Ca2+ activation of force generation by skinned diaphragmatic myofilaments, and the phosphorylation of myofilament proteins. Results demonstrate that myofilament force production, and the Ca2+ sensitivity of force generation, were not impacted by acclimation to hypobaric hypoxia, and did not differ between preparations from the two species. The cooperativity of the force-pCa relationship, and the maximal rate of force generation were also the same in the preparations from both species, and not impacted by acclimation. Finally, the relative phosphorylation of TnT, and MLC was lower in deer mice than white-footed mice, but was not affected by acclimation. These results indicate that species differences in diaphragm function, and the increase in force production with hypoxia acclimation, are not due to differences, or changes, in myofilament function. However, it appears that diaphragmatic myofilament function in these species is not affected by chronic hypobaric hypoxia exposure.

Molar crenulation trait definition and variation in modern human populations.

Crenulated molars have been used extensively in biological anthropology. However, the trait has not been formally defined, nor have population frequencies been thoroughly outlined. This study provides a formal definition of molar crenulations and data on their presence in a large sample. Data were collected on maxillary and mandibular molars of modern dental material from various populations: South African, Hispanic, Japanese, American White, and American Black (n = 750). Molar crenulations were defined and a rank-scale created. Statistical analyses include chi-squared, correspondence analysis, and trait correlations. Significant statistical differences were found between populations in all molars. Minimal sexual dimorphism was noted, and is most pronounced among the American Black sample. Generally, American White and Japanese samples showed lower frequencies of molar crenulations, the highest frequencies were seen in the American Black and South African samples, and the Hispanic sample was intermediate. Correspondence analysis showed that American Black samples tended towards grade 2, and South African samples were more often a grade 1. American White and Japanese samples were most often grade 0, and Hispanic samples were intermediate. Correlations were noted across the molars. Population differences exist in the presence of molar crenulations, which were likely shaped by evolution. Based on these results molar crenulations can be added to the suite of traits currently used to study population differences.

Unilateral absence of mandibular condyle in a Bronze Age male skeleton from Portugal.

In 2009, a pit burial dated to the Bronze Age was excavated in Monte do Gato de Cima 3 (Portugal). The purpose of this paper is to describe the pathological absence of the left mandibular condyle noted in an adult male skeleton and to discuss possible diagnoses, including subcondylar fracture, cystic defect, congenital absence, condylar aplasia and mandibular condylysis. The most likely explanation for the pathological alteration is subcondylar fracture with non-union. Although the occurrence of non-union and slight osteoarthritic alterations in the left glenoid fossa were evident, this mandible was likely functional, as can be inferred from dental wear and muscle attachment sites. This trauma probably occurred before adult age when remodelling capacity is still high. Thus, bones and muscles adequately compensated for the trauma and only minor asymmetry developed. Consequently, this injury seems not to have greatly influenced masticatory functions. This is in accordance with clinical data, which demonstrate that, in growing patients, conservative treatment (non-surgical) results in good remodelling and patient recovery. In addition, in the few paleopathological cases published, the healing capacity of these types of mandibular fractures seems to be good, as can be inferred by evidence from the bone.

Effects of chronic hypoxia on diaphragm function in deer mice native to high altitude.

AIM: We examined the effects of chronic hypoxia on diaphragm function in high- and low-altitude populations of Peromyscus mice. METHODS: Deer mice (P. maniculatus) native to high altitude and congeneric mice native to low altitude (P. leucopus) were born and raised in captivity to adulthood and were acclimated to normoxia or hypobaric hypoxia (12 or 9 kPa, simulating hypoxia at 4300 and 7000 m) for 6-8 weeks. We then measured indices of mitochondrial respiration capacity, force production, and fatigue resistance in the diaphragm. RESULTS: Mitochondrial respiratory capacities (assessed using permeabilized fibres with single or multiple inputs to the electron transport system), citrate synthase activity (a marker of mitochondrial volume), twitch force production, and muscle fatigue resistance increased after exposure to chronic hypoxia in both populations. These changes were not well explained by variation in the fibre-type composition of the muscle. However, there were several differences in diaphragm function in high-altitude mice compared to low-altitude mice. Exposure to a deeper level of hypoxia (9 kPa vs 12 kPa) was needed to elicit increases in mitochondrial respiration rates in highlanders. Chronic hypoxia did not increase the emission of reactive oxygen species from permeabilized fibres in highlanders, in contrast to the pronounced increases that occurred in lowlanders. In general, the diaphragm of high-altitude mice had greater capillary length densities, produced less force in response to stimulation and had shorter relaxation times. The latter was associated with higher activity of sarcoplasmic reticulum Ca2+ -ATPase (SERCA) activity in the diaphragm of high-altitude mice. CONCLUSION: Overall, our work suggests that exposure to chronic hypoxia increases the capacities for mitochondrial respiration, force production and fatigue resistance of the diaphragm. However, many of these effects are opposed by evolved changes in diaphragm function in high-altitude natives, such that highlanders in chronic hypoxia maintain similar diaphragm function to lowlanders in sea level conditions.

Control of breathing and ventilatory acclimatization to hypoxia in deer mice native to high altitudes.

AIM: We compared the control of breathing and heart rate by hypoxia between high- and low-altitude populations of Peromyscus mice, to help elucidate the physiological specializations that help high-altitude natives cope with O2 limitation. METHODS: Deer mice (Peromyscus maniculatus) native to high altitude and congeneric mice native to low altitude (Peromyscus leucopus) were bred in captivity at sea level. The F1 progeny of each population were raised to adulthood and then acclimated to normoxia or hypobaric hypoxia (12 kPa, simulating hypoxia at ~4300 m) for 5 months. Responses to acute hypoxia were then measured during stepwise reductions in inspired O2 fraction. RESULTS: Lowlanders exhibited ventilatory acclimatization to hypoxia (VAH), in which hypoxia acclimation enhanced the hypoxic ventilatory response, made breathing pattern more effective (higher tidal volumes and lower breathing frequencies at a given total ventilation), increased arterial O2 saturation and heart rate during acute hypoxia, augmented respiratory water loss and led to significant growth of the carotid body. In contrast, highlanders did not exhibit VAH - exhibiting a fixed increase in breathing that was similar to hypoxia-acclimated lowlanders - and they maintained even higher arterial O2 saturations in hypoxia. However, the carotid bodies of highlanders were not enlarged by hypoxia acclimation and were similar in size to those of normoxic lowlanders. Highlanders also maintained consistently higher heart rates than lowlanders during acute hypoxia. CONCLUSIONS: Our results suggest that highland deer mice have evolved high rates of alveolar ventilation and respiratory O2 uptake without the significant enlargement of the carotid bodies that is typical of VAH in lowlanders, possibly to adjust the hypoxic chemoreflex for life in high-altitude hypoxia.

The roller coaster flight strategy of bar-headed geese conserves energy during Himalayan migrations.

The physiological and biomechanical requirements of flight at high altitude have been the subject of much interest. Here, we uncover a steep relation between heart rate and wingbeat frequency (raised to the exponent 3.5) and estimated metabolic power and wingbeat frequency (exponent 7) of migratory bar-headed geese. Flight costs increase more rapidly than anticipated as air density declines, which overturns prevailing expectations that this species should maintain high-altitude flight when traversing the Himalayas. Instead, a "roller coaster" strategy, of tracking the underlying terrain and discarding large altitude gains only to recoup them later in the flight with occasional benefits from orographic lift, is shown to be energetically advantageous for flights over the Himalayas.

The paradox of extreme high-altitude migration in bar-headed geese Anser indicus.

Bar-headed geese are renowned for migratory flights at extremely high altitudes over the world's tallest mountains, the Himalayas, where partial pressure of oxygen is dramatically reduced while flight costs, in terms of rate of oxygen consumption, are greatly increased. Such a mismatch is paradoxical, and it is not clear why geese might fly higher than is absolutely necessary. In addition, direct empirical measurements of high-altitude flight are lacking. We test whether migrating bar-headed geese actually minimize flight altitude and make use of favourable winds to reduce flight costs. By tracking 91 geese, we show that these birds typically travel through the valleys of the Himalayas and not over the summits. We report maximum flight altitudes of 7290 m and 6540 m for southbound and northbound geese, respectively, but with 95 per cent of locations received from less than 5489 m. Geese travelled along a route that was 112 km longer than the great circle (shortest distance) route, with transit ground speeds suggesting that they rarely profited from tailwinds. Bar-headed geese from these eastern populations generally travel only as high as the terrain beneath them dictates and rarely in profitable winds. Nevertheless, their migration represents an enormous challenge in conditions where humans and other mammals are only able to operate at levels well below their sea-level maxima.

European guideline for the management of scabies, 2010.

Transmission of the mite Sarcoptes scabiei generally occurs by protracted direct body contact; although in crusted scabies, transmission also occurs via infected clothing or bedding. Diagnosis is usually clinical and topical antiscabietics are the mainstay of treatment. Oral ivermectin is not licensed in most countries, but may have a role in certain patients. Treatment of sexual contacts is indicated.

European guideline for the management of pediculosis pubis, 2010.

Transmission of the crab louse Phthirus pubis generally occurs by close body contact. Diagnosis is usually clinical and screening for other sexually transmitted infections (STIs) is indicated. While most evidence is extrapolated from studies of head lice treatments, topical pediculicides are recommended and treatment of sexual contacts is indicated.

General practitioner involvement and patient outcomes in HIV management.

We undertook this study to try to determine whether disease outcomes were poorer in patients with HIV infection whose general practitioner (GP) was unaware of their status compared with those whose GP was aware. The notes of 375 HIV-positive patients attending Edinburgh's genitourinary (GU) medicine clinic were reviewed. The GPs of 292 patients (78%) had been informed of their patient's HIV infection. Advancing disease was associated with disclosure of the status to GPs (P = 0.037) but no significant association was found between informing GPs and the viral load results of treated (P = 0.389) and untreated patients (P = 0.070). Twenty-three percent of patients had had one or more bacterial sexually transmitted infections (STIs) while receiving their HIV care at a GU medicine clinic. Patients diagnosed with an STI were less likely to disclose their HIV status to their GP (P < 0.0005). Non-disclosure of the HIV status to a GP may be a predictor of unsafe sexual practices.

Structure and regulation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in killifish: A comparative genomics approach.

The structure, regulation and evolution of the cystic fibrosis transmembrane conductance regulator (CFTR) gene were characterized in common killifish (Fundulus heteroclitus). Killifish CFTR (kfCFTR) structure was conserved with other CFTR homologues, but was more compact than those of mammals. A motif in intron 1 was conserved across all teleost CFTR homologues except zebrafish, and was similar to a functionally important site in human CFTR. The sequence of the CFTR promoter was highly conserved across nine species within the genus Fundulus, but contained additional glucocorticoid responsive elements in seawater species. The promoters of the seawater species also contained a putative osmotic responsive element that differed by a single base in the freshwater species. The kfCFTR promoter was only active in cell lines that express the endogenous CFTR gene. Transcription from the kfCFTR promoter was unaffected by application of dexamethasone or cortisol in cell culture, but increased by 1.5-fold in response to high osmolarity. Cortisol injection in vivo increased CFTR mRNA but there was no increase in luciferase expression driven by the kfCFTR promoter in transiently transgenic fish. Administration of the cortisol blocker RU486 resulted in a significant reduction in luciferase activity driven by the kfCFTR promoter in vivo.

Audit on the management of epididymo-orchitis by the Department of Urology in Edinburgh.

Epididymo-orchitis among men younger than 35 years is mainly caused by chlamydial infection. National guidelines for the management of this condition have been published. The aim of this study was to audit the management of epididymo-orchitis in a major teaching hospital. To this end we performed a retrospective study of patients with epididymo-orchitis admitted to the Department of Urology in the Western General Hospital, Edinburgh between 1998 and 2003. Case-notes of 108 cases of epididymo-orchitis were reviewed. The diagnosis was established by ultrasound in 94% of cases. Patients were not tested routinely for chlamydial infection and the majority of men younger than 35 years were treated inappropriately with ciprofloxacin. The management of patients younger than 35 years was not in accordance with the recommendations of national guidelines. Chlamydia trachomatis is sexually transmissible and is not responsive to ciprofloxacin. As a result of this audit, each patient will be tested for chlamydial infection and men younger than 35 years will be treated with ofloxacin. Sexual partners of patients with chlamydial infection will be treated in the department of genitourinary medicine.

What is the role of scrotal ultrasound scans in genitourinary medicine?

The objective of the study was to review the indications for scrotal ultrasound scans and to assess the impact on patient management. We therefore performed a retrospective analysis. Case notes of all males referred for a scrotal ultrasound between April 1998 and March 2001 were studied. Data were extracted for the following: age, presenting complaints, physical findings on examination, results of a full sexual screen, treatment, ultrasound result and the designation of the person requesting the scan. All data were tabulated and summated using 'Windows Excel' software. One hundred and fifteen men were referred for an ultrasound in this period of time. None had an ultrasound more than once. Of these, 25 subjects could not be included as they either failed to attend for their scan (n=8) or their notes could not be traced (n=17). Twelve subjects were excluded as they did not fit the selection criteria (n=12). Median age was 30 years (Range 19-61 years). The commonest reason for referral was testicular pain (n=43) followed by testicular lump (n=19). The commonest abnormality on examination was an inflamed epididymis (n=18). Forty-two of the ultrasound scans were normal. A testicular mass was detected in only five of the 78 patients (6.4%), of which one was a malignancy (1.2%). A direct referral to a urologist for further management was made in only nine patients. Scrotal ultrasound for pain has limited impact on patient management apart from reassuring a worried patient. However, it remains an important investigation in the management of a suspected testicular lump.

Infection of the CD45RA+ (naive) subset of peripheral CD8+ lymphocytes by human immunodeficiency virus type 1 in vivo.

To investigate the mechanism and functional significance of infection of CD8+ lymphocytes by human immunodeficiency virus type 1 (HIV-1) in vivo, we determined frequencies of infection, proviral conformation, and genetic relationships between HIV-1 variants infecting naive (CD45RA+) and memory (CD45RO+) peripheral blood CD4+ and CD8+ lymphocytes. Infection of CD3+ CD8+ CD45RA+ cells was detected in 9 of 16 study subjects at frequencies ranging from 30 to 1,400 proviral copies/10(6) cells, more frequently than CD3+ CD8+ lymphocytes expressing the RO isoform of CD45 (n = 2, 70 and 260 copies /10(6) cells). In agreement with previous studies, there was no evidence for a similar preferential infection of CD4+ naive lymphocytes. Proviral sequences in both CD4+ and CD8+ lymphocyte subsets were complete, as assessed by quantitation using primers from the long terminal repeat region spanning the tRNA primer binding site. In six of the seven study subjects investigated, variants infecting CD8+ lymphocytes were partially or completely genetically distinct in the V3 region from those recovered from CD4+ lymphocytes and showed a greater degree of compartmentalization than observed between naive and memory subsets of CD4+ lymphocytes. In two study subjects, arginine substitutions at position 306, associated with use of the chemokine coreceptor CXCR4, were preferentially found in CD4 lymphocytes. These population differences may have originated through different times of infection rather than necessarily indicating a difference in their biological properties. The preferential distribution of HIV-1 in naive CD8+ lymphocytes indeed suggests that infection occurred early in T-lymphocyte ontogeny, such as during maturation in the thymus. Destruction of cells destined to become CD8+ lymphocytes may be a major factor in the decline in CD8+ lymphocyte frequencies and function on disease progression and may contribute directly to the observed immunodeficiency in AIDS.

Antiretroviral therapy in HIV infection: are we using resources appropriately and cost effectively?

The provision of antiretroviral therapy to HIV-positive patients attending the Department of Genitourinary Medicine at the Royal Infirmary of Edinburgh was assessed, to examine whether clinicians were offering treatment in line with the departmental protocol. A total of 195 patients attended in 1998, of whom 169 fulfilled the protocol criteria for treatment. Although only 115 of these were on therapy, no patient who fulfilled treatment criteria and wished to be treated was denied treatment. Of the 26 patients not fulfilling any treatment criteria, 9 had transferred in from another unit already on treatment. The remaining 17 were not on treatment.