Living with AIDS in Uganda: a qualitative study of patients' and families' experiences following referral to hospice

Background: Globally, the majority of people with HIV/AIDS live in sub-Saharan Africa. While the increasing availability of antiretroviral therapy is improving the outlook for many, its effects are yet to reach all of those in need and patients still present with advanced disease. This paper reports findings from qualitative interviews with patients living with AIDS and their caregivers who were receiving palliative care from Hospice Africa Uganda (HAU). We aimed to understand what motivated patients and their families to seek formal healthcare, whether there were any barriers to help- seeking and how the help and support provided to them by HAU was perceived. Methods: We invited patients with AIDS and their relatives who were newly referred to HAU to participate in qualitative interviews. Patients and carers were interviewed in their homes approximately four weeks after the patient’s enrolment at HAU. Interviews were translated, transcribed and analysed using narrative and thematic approaches. Results: Interviews were completed with 22 patients (10 women and 12 men) and 20 family caregivers, nominated by patients. Interviews revealed the extent of suffering patients endured and the strain that family caregivers experienced before help was sought or accessed. Patients reported a wide range of severe physical symptoms. Patients and their relatives reported worries about the disclosure of the AIDS diagnosis and fear of stigma. Profound poverty framed all accounts. Poverty and stigma were, depending on the patient and family situation, both motivators and barriers to help seeking behaviour. Hospice services were perceived to provide essential relief of pain and symptoms, as well as providing rehabilitative support and a sense of caring. The hospice was perceived relieve utter destitution, although it was unable to meet all the expectations that patients had. Conclusion: Hospice care was highly valued and perceived to effectively manage problems such as pain and other symptoms and to provide rehabilitation. Participants noted a strong sense of being “cared for”. However, poverty and a sense of stigma were widespread. Further research is needed to understand how poverty and stigma can be effectively managed in hospice care for patients for advanced AIDS and their families

The Effect Of Hip Position/Configuration On EMG Patterns In Cycling

From the results of previous investigations examining the effect of changes in hip angles on cycling performance, it had been concluded that there is an optimal hip position/configuration which maximizes aerobic and anaerobic work. But why and how this hip position/configuration affects cycling perfonnance is unknown. Therefore, it was the purpose of this investigation to determine whether differences in cycling performance with changes in hip position/configurations are reflected and can be explaincd by changes in EMG patterns. Five male recreational cyclists were tested in 5 different hip position/configuration (0,25,50,75, and 100 degrees), as defined by the angie formed between the bicycle seat tube and a vertical line (perpendicular to the ground) passing through the pedal axis. By rotating the seat to maintain a backrest perpendicular to the ground, a systematic decrease in hip angle from the 0 to 100 degree position was induced. For each condition, the seat to pedal distance was adjusted to remain 100% (to within 3/4 inch or 1.905 cm) of the total leg length, as measured from the greater trochanter of the femur of the right leg to the ground. In each position, the minimum and maximum hip, knee, and ankle angles were obtained for one complete pedal revolution. A cycle ergometer was used with a resistance of 65 gm/kg of the subject'S body mass (3.82 joules/pedal rev/kg BM) at a pedaling frequency of 60 rpm. Each subject was strapped to the seat-backrest at the waist and hips, and pedal toeclips were worn. For each test condition, EMG activity of 6 muscle groups of the right limb were each collected at a rate of 2000 Hz with surface electrodes. A recorder and a micro-switch interfaced to a microcomputer was used to record EMG activity and pedal position. For a complete pedal cycle in each hip position, a waveform data analysis program was used to determine: (l) the sequence of activity by the different muscle groups; (2) the duration of activity; and (3) the pedal position each muscle group was active and inactive. ReANOVA's and post-hoc tests revealed significant differences in the pedal position location that the rectus femoris, gluteus maximus, vastus medialis and biceps femoris were active and inactive during a pedal cycle with changes in hip position/configuration. With a systematic change in hip position from 0 to 100 degrees, there is a backward shift in pedal position loca tion that the muscles were active and inactive. It was concluded that differences in cycling performance with changes in hip position/configuration are reflected and can be explained by differences in EMG patterns. Supported by a grant-in-aid of research from Sigma XI, The Scientific Research Society

THE EFFECT OF PEDAL CRANKARM LENGTH ON POWER PRODUCTION IN RECUMBENT CYCLE ERGOMETRY

In human powered vehicles, adjustments in seat-to-pedal distance, seat tube angle, and body orientation (trunk angle with respect to the ground) will result in changes in hip, knee, and ankle angles. Changes in these joint angles often affect cycling performance by altering muscle length, moment arm length, angle of pull, joint range of motion, and/or the force/torque/power generated by different muscle groups. How changes in crankarm length affect joint kinematics and cycling performance has not been examined. Therefore, the purpose of this investigation was to determine the effect of changes in pedal crankarm length on joint kinematics and power production in recumbent cycle ergometry. Twenty healthy volunteer male subjects (mean age = 24.8 yrs, SD = 4.4 yrs) were tested in five pedal crankarm length (1 10, 145,180,230, and 265 mm) according to a randomized sequence (with a minimum of 24 hours rest between test sessions), using a free weight Monark bicycle ergometer (Model 814E). A variable seating apparatus was constructed and used, with the seat-to-pedal distance adjusted to 100% of each subject's leg length (as measured from the greater trochanter of the right leg to the ground). Pedal toe-clips were worn, and each subject's upper body was kept perpendicular to the ground. In each condition, the minimum and maximum hip, knee, and ankle angles were measured for one complete pedal revolution. A computerized 30 second Wingate anaerobic cycling test was used, with a resistance of 85 gm/kg of each subject's body mass (5.0 joules/pedal rev/kg BM). Peak power (5 sec) and mean power (30 sec) were determined by a SMI Power Program (Sports Medicine Industries). DM MANOVAs and post-hoc tests revealed that (1) hip, knee and ankle angles changed significantly with changes in crankarm length (p < .01); (2) peak power in the 110 and 145 mm crankarm lengths were significantly greater than that in the other lengths (p < .05); and (3) mean power in the 180 mm crankarrn length was significantly greater than that in the 1 10, 230 and 265 mm condition (p < .05). With increasing crankarm lengths, there is decrement in mean joint angles (hip, knee, and ankle), an increment in joint range of motion, a decrement in peak power, and a curvilinear end in mean power. Changes in pedal crankarm length by 35 mm will significantly alter joint kinematics to affect cycling performance, as evidenced by changes in peak and mean power. The shortest crankarrn length (1 10 mm) resulted in the largest peak power production (and fatigue index), whereas the middle crankarm length (180 mm) resulted in the largest mean power production. It was concluded that the optimal crankarm length to maximize performance in recumbent cycle ergometry will be dependent on the goal of the activity. - This research was supported by a grant from the UNLV Research Grants and Fellowship Committee

Lethal Mutagenesis of Picornaviruses with N-6-Modified Purine Nucleoside Analogues

RNA viruses exhibit extraordinarily high mutation rates during genome replication. Nonnatural ribonucleosides that can increase the mutation rate of RNA viruses by acting as ambiguous substrates during replication have been explored as antiviral agents acting through lethal mutagenesis. We have synthesized novel N-6-substituted purine analogues with ambiguous incorporation characteristics due to tautomerization of the nucleobase. The most potent of these analogues reduced the titer of poliovirus (PV) and coxsackievirus (CVB3) over 1,000-fold during a single passage in HeLa cell culture, with an increase in transition mutation frequency up to 65-fold. Kinetic analysis of incorporation by the PV polymerase indicated that these analogues were templated ambiguously with increased efficiency compared to the known mutagenic nucleoside ribavirin. Notably, these nucleosides were not efficient substrates for cellular ribonucleotide reductase in vitro, suggesting that conversion to the deoxyriboucleoside may be hindered, potentially limiting genetic damage to the host cell. Furthermore, a high-fidelity PV variant (G64S) displayed resistance to the antiviral effect and mutagenic potential of these analogues. These purine nucleoside analogues represent promising lead compounds in the development of clinically useful antiviral therapies based on the strategy of lethal mutagenesis

Lethal Mutagenesis of Poliovirus Mediated by a Mutagenic Pyrimidine Analogue

Lethal mutagenesis is the mechanism of action of ribavirin against poliovirus (PV) and numerous other RNA viruses. However, there is still considerable debate regarding the mechanism of action of ribavirin against a variety of RNA viruses. Here we show by using T7 RNA polymerase mediated production of PV genomic RNA, PV polymerase-catalyzed primer extension and cell-free PV synthesis that a pyrimidine ribonucleoside triphosphate analogue (rPTP) with ambiguous basepairing capacity is an efficient mutagen of the PV genome. The in vitro incorporation properties of rPTP are superior to ribavirin triphosphate. We observed a log-linear relationship between virus titer reduction and the number of rPMP molecules incorporated. A PV genome encoding a high-fidelity polymerase was more sensitive to rPMP incorporation, consistent with diminished mutational robustness of high-fidelity PV. The nucleoside (rP) did not exhibit antiviral activity in cell culture owing to the inability of rP to be converted to rPMP by cellular nucleotide kinases. rP was also a poor substrate for herpes simplex virus thymidine kinase. The block to nucleoside phosphorylation could be bypassed by treatment with the P nucleobase, which exhibited both antiviral activity and mutagenesis, presumably a reflection of rP nucleotide formation by a nucleotide salvage pathway. These studies provide additional support for lethal mutagenesis as an antiviral strategy, suggest that rPMP prodrugs may be highly efficacious antiviral agents, and provide a new tool to determine the sensitivity of RNA virus genomes to mutagenesis as well as interrogation of the impact of mutational load on the population dynamics of these viruses

The Effect of Pedal Crank Arm Length and Seat Height on Joint Angles in an Upright Cycling Position

Manipulations in crank arm length and seat height have resulted in significant changes in cycling performance. To better understand how these manipulations affect cycling performance, the purpose of this investigation was to determine the effect of 5 pedal crank arm lengths (l10, 145, 180, 215 and 250 mm) and 3 seat height (short, medium, and long) on joint angles (minimum, maximum, and range of motion) of the hip, knee, and ankle, as determined by 3 in an upright cycling position for 7 male participants. Nine 5 x 3 Repeated Measures Factor ANOVAs revealed that 35 mm increments in crank arm length from I l0-250mm resulted in a significant (p < 0.01): (1) decrement int he minimum hip and knee angle; (2) increment in the minimum ankle angle; (3) increment in the hip and knee range of motion; and (4) decrement in the ankle range of motion. It was determined that 6 cm changes in seat height from the shortest to the longest seat height resulted in a significant (p < 0.01): (l) increment in the minimum and maximum joint angle of the hip, knee, and ankle; and (2) increment in the range of motion of the knee. No significant interactions were found between crank arm length and seat height for different angle measurements (minimum, maximum, and range of motion) of the hip, knee, and ankle. In conjunction with the results of previous investigations, certain joint angle ranges result in more effective cycling performance.SUNY BrockportKinesiology, Sport Studies and Physical Education Faculty Publication

The Effect of Pedal Crank Arm Length on Lower Limb Joint Angles in an Upright Cycling Position

The purpose of this investigation was to determine whether changes in CAL resulted in significant changes in joint angles, and how these changes are related to changes in cycling performance

Determination of the Crank-arm Length to Maximize Power Production in Recumbent Cycle Ergometry

Originally published in Human Power: Technical Journal of the IHPVA.The purpose of this study was to determine the crank-arm length that would maximize peak, mean and minimum power outputs in a recumbent cycling position. Nineteen male volunteers were each tested with five pedal crank-arm lengths (110, 145, 180,230 and 265 mm) according to a randomized sequence on a free-weight Monark cycle ergometer. The 30-second Wingate Anaerobic Cycling test was performed in a recumbent position (750 seat-tube angle, backrest perpendicular to the ground) against a resistance of 85 g/kg of the subject's body mass (5.0 J/crank rev/kg BM). Curve estimation with regression analysis revealed that the crank-arm lengths to maximize peak power, mean power and minimum power are J24 mm, 175 mm and 215 mm, respectively.SUNY BrockportKinesiology, Sport Studies and Physical Education Faculty Publication