ABSTRACT
BACKGROUND: Women with HIV are globally underrepresented in clinical research. Existing studies often focus on reproductive outcomes, seldom focus on older women, and are often underpowered to assess sex/gender differences. We describe CD4, HIV viral load (VL), clinical characteristics, comorbidity burden, and use of antiretroviral therapy (ART) among women with HIV in the RESPOND study and compare them with those of the men in RESPOND. METHODS: RESPOND is a prospective, multi-cohort collaboration including over 34 000 people with HIV from across Europe and Australia. Demographic and clinical characteristics, including CD4/VL, comorbidity burden, and ART are presented at baseline, defined as the latter of 1 January 2012 or enrolment into the local cohort, stratified by age and sex/gender. We further stratify men by reported mode of HIV acquisition, men who have sex with men (MSM) and non-MSM. RESULTS: Women account for 26.0% (n = 9019) of the cohort, with a median age of 42.2 years (interquartile range [IQR] 34.7-49.1). The majority (59.3%) of women were white, followed by 30.3% Black. Most women (75.8%) had acquired HIV heterosexually and 15.9% via injecting drug use. Nearly half (44.8%) were receiving a boosted protease inhibitor, 31.4% a non-nucleoside reverse transcriptase inhibitor, and 7.8% an integrase strand transfer inhibitor. The baseline year was 2012 for 73.2% of women and >2019 for 4.2%. Median CD4 was 523 (IQR 350-722) cells/µl, and 73.6% of women had a VL <200 copies/mL. Among the ART-naïve population, women were more likely than MSM but less likely than non-MSM (p < 0.001) to have CD4 <200 cells/µL and less likely than both MSM and non-MSM (p < 0.001) to have VL ≥100 000 copies/mL. Women were also more likely to be free of comorbidity than were both MSM and non-MSM (p < 0.0001). CONCLUSION: RESPOND women are diverse in age, ethnicity/race, CD4/VL, and comorbidity burden, with important differences relative to men. This work highlights the importance of stratification by sex/gender for future research that may help improve screening and management guidelines specifically for women with HIV.
ABSTRACT
A critical shortage of trained cancer specialists is one of the major challenges in addressing the increasing cancer burden in low- and middle-income countries. Inadequate undergraduate cancer education in oncology remains a major obstacle for both task shifting to general practitioners and for training of specialists. We provide the first report of cancer education in Rwanda's undergraduate program to survey how new graduates are prepared to provide care for cancer patients. Anonymous online survey was sent January to June 2017 to medical students in their senior clinical years (years 5 and 6). Questions related to the demographics, medical curriculum, and general oncology exposure were included in the survey. Of 192 eligible students, 42% (n = 80) completed the survey and were analyzed. The majority were 25 to 29 years of age and 41% were female. Internal medicine was cited to provide the most exposure to cancer patients (50%) and cancer bedside teaching (55%). Close to a half (46%) have been taught oncology formally in addition to bedside teaching. A tenth (11%) of the participants felt comfortable in attending a cancer patient, and a fifth (21%) of the students felt comfortable while addressing multimodality treatment approach. The majority (99%) of the participants preferred having a formal oncology rotation. Of particular interest, 61% of the students are interested in pursuing an oncology career path. There is a need to modify the current oncology undergraduate curriculum to prepare future physicians for delivering cancer care in Rwanda. Raising the profile of oncology in undergraduate medical education will complement the on-going efforts to increase the country's capacity in task shifting and in training of cancer specialists.
Subject(s)
Curriculum/standards , Education, Medical, Undergraduate/methods , Medical Oncology/education , Neoplasms/therapy , Specialization/statistics & numerical data , Students, Medical/psychology , Adult , Cross-Sectional Studies , Female , Humans , Male , RwandaABSTRACT
Populations of fishes provide valuable services for billions of people, but face diverse and interacting threats that jeopardize their sustainability. Human population growth and intensifying resource use for food, water, energy and goods are compromising fish populations through a variety of mechanisms, including overfishing, habitat degradation and declines in water quality. The important challenges raised by these issues have been recognized and have led to considerable advances over past decades in managing and mitigating threats to fishes worldwide. In this review, we identify the major threats faced by fish populations alongside recent advances that are helping to address these issues. There are very significant efforts worldwide directed towards ensuring a sustainable future for the world's fishes and fisheries and those who rely on them. Although considerable challenges remain, by drawing attention to successful mitigation of threats to fish and fisheries we hope to provide the encouragement and direction that will allow these challenges to be overcome in the future.
Subject(s)
Conservation of Natural Resources/methods , Fisheries , Fishes/physiology , Animals , Ecosystem , Fishes/growth & development , Population Dynamics , Water QualityABSTRACT
BACKGROUND: Huntington disease (HD) has most recently been estimated to affect between 10.6 and 13.7 per 100,000 individuals in European populations. However, prevalence is known to differ geographically. In South Africa, the only published estimates are from a survey performed in the 1970s, an era when the disease was believed to be rare or absent in black individuals and molecular confirmation was absent. The disease phenotype in South Africa is currently attributable to mutations in both the huntington and junctophilin-3 genes, which underlie the well-known HD and the rarer HD-like 2 (HDL2) respectively. This study aimed at providing improved minimum estimates of disease frequency in South Africa, based on molecular genetic testing data. METHODS: A review of all testing records for HD and HDL2 over a 20-year period was undertaken. HDL2 is virtually indistinguishable on clinical features, thus necessitating its inclusion. RESULTS: Based on molecular diagnostic records, minimum estimates of disease frequency are: 5.1, 2.1 and 0.25 (per 100,000 individuals) for the white, mixed ancestry and black population groups respectively. CONCLUSION: Although ascertainment remains incomplete, these minimum estimates suggest that disease frequencies are significantly higher than those previously reported in South Africa.
Subject(s)
Black People , Chorea/epidemiology , Cognition Disorders/epidemiology , Dementia/epidemiology , Heredodegenerative Disorders, Nervous System/epidemiology , Huntington Disease/epidemiology , Population Surveillance , White People , Black People/genetics , Chorea/diagnosis , Chorea/genetics , Cognition Disorders/diagnosis , Cognition Disorders/genetics , Dementia/diagnosis , Dementia/genetics , Gene Frequency/genetics , Heredodegenerative Disorders, Nervous System/diagnosis , Heredodegenerative Disorders, Nervous System/genetics , Humans , Huntington Disease/diagnosis , Huntington Disease/genetics , Retrospective Studies , South Africa/epidemiology , White People/geneticsABSTRACT
The migratory behaviour of hatchery-reared landlocked Atlantic salmon Salmo salar raised under three different feeding regimes was monitored through the lower part of the River Klarälven, Sweden. The smolts were implanted with acoustic transmitters and released into the River Klarälven, 25 km upstream of the outlet in Lake Vänern. Early mature males, which had matured the previous autumn, were also tagged and released. To monitor migration of the fish, acoustic receivers were deployed along the migratory route. The proportion of S. salar that reached Lake Vänern was significantly greater for fish fed fat-reduced feed than for fish given rations with higher fat content, regardless of ration size. Fish from the early mature male group remained in the river to a greater extent than fish from the three feeding regimes. Smolt status (degree of silvering), as visually assessed, did not differ among the feeding regime groups, and moreover, fully-silvered fish, regardless of feeding regime, migrated faster and had a greater migration success than fish with less developed smolt characteristics. Also, successful migrants had a lower condition factor than unsuccessful ones. These results indicate that the migration success of hatchery-reared S. smolts released to the wild can be enhanced by relatively simple changes in feeding regimes and by matching stocking time with smolt development.
Subject(s)
Animal Migration , Aquaculture/methods , Feeding Behavior , Salmo salar/physiology , Animal Identification Systems , Animals , Male , Rivers , SwedenABSTRACT
The effects of feed quality and quantity on growth, early male parr maturation and development of smolt characteristics were studied in hatchery-reared landlocked Atlantic salmon Salmo salar. The fish were subjected to two levels of feed rations and two levels of lipid content from first feeding until release in May of their second year. Salmo salar fed high rations, regardless of lipid content, grew the most and those fed low lipid feed with low rations grew the least. In addition, fish fed low lipid feed had lower body lipid levels than fish fed high lipid feed. Salmo salar from all treatments showed some reduction in condition factor (K) and lipid levels during their second spring. Smolt status was evaluated using both physiological and morphological variables. These results, based on gill Na(+) , K(+) -ATPase (NKA) enzyme activity, saltwater tolerance challenges and visual assessments, were consistent with each other, showing that S. salar from all treatments, except the treatment in which the fish were fed low rations with low lipid content, exhibited characteristics associated with smolting at 2 years of age. Sexually mature male parr from the high ration, high lipid content treatment were also subjected to saltwater challenge tests, and were found to be unable to regulate plasma sodium levels. The proportion of sexually mature male parr was reduced when the fish were fed low feed rations, but was not affected by the lipid content of the feed. Salmo salar fed low rations with low lipid content exhibited the highest degree of severe fin erosion.
Subject(s)
Animal Feed , Aquaculture , Salmo salar/growth & development , Animals , Body Size , Dietary Fats/administration & dosage , Gills/enzymology , Male , Salmo salar/physiology , Seawater , Sexual Maturation , Sodium-Potassium-Exchanging ATPase/metabolismABSTRACT
PURPOSE: Based on the previous indications of founder ATP-binding cassette sub-family A member 4 gene (ABCA4) mutations in a South African subpopulation, the purpose was to devise a mechanism for identifying common disease-causing mutations in subjects with ABCA4-associated retinopathies (AARs). Facilitating patient access to this data and determining the frequencies of the mutations in the South African population would enhance the current molecular diagnostic service offered. METHODS: The majority of subjects in this study were of Caucasian ancestry and affected with Stargardt macular dystrophy. The initial cohort consisted of DNA samples from 181 patients, and was screened using the ABCR400 chip. An assay was then designed to screen a secondary cohort of 72 patients for seven of the most commonly occurring ABCA4 mutations in this population. A total of 269 control individuals were also screened for the seven ABCA4 mutations. RESULTS: Microarray screening results from a cohort of 181 patients affected with AARs revealed that seven ABCA4 mutations (p.Arg152*, c.768G>T, p.Arg602Trp, p.Gly863Ala, p.Cys1490Tyr, c.5461-10T>C, and p.Leu2027Phe) occurred at a relatively high frequency. The newly designed genetic assay identified two of the seven disease-associated mutations in 28/72 patients in a secondary patient cohort. In the control cohort, 12/269 individuals were found to be heterozygotes, resulting in an estimated background frequency of these mutations in this particular population of 4.46 per 100 individuals. CONCLUSIONS: The relatively high detection rate of seven ABCA4 mutations in the primary patient cohort led to the design and subsequent utility of a multiplex assay. This assay can be used as a viable screening tool and to reduce costs and laboratory time. The estimated background frequency of the seven ABCA4 mutations, together with the improved diagnostic service, could be used by counselors to facilitate clinical and genetic management of South African families with AARs.
Subject(s)
ATP-Binding Cassette Transporters/genetics , Macular Degeneration/genetics , Mutation , Base Sequence , Case-Control Studies , Exons , Female , Genetic Testing , Humans , Macular Degeneration/congenital , Male , Molecular Sequence Data , Oligonucleotide Array Sequence Analysis , Pedigree , Risk Factors , South Africa , Stargardt Disease , White PeopleABSTRACT
Prey capture success and foraging mode were studied in brown trout Salmo trutta at temperatures ranging from 5.7 to 14.0° C. At low temperatures, there was a positive correlation between prey capture success and the proportion of time that the fish spent holding feeding stations. This correlation was not found at temperatures >10° C.
Subject(s)
Appetitive Behavior/physiology , Predatory Behavior/physiology , Temperature , Trout/physiology , AnimalsABSTRACT
Lymphocytes, from randomly selected individuals having normal immune function, when incubated in vitro with varying concentrations of streptococcal antigens, responded in three ways: (a) response over the entire antigen concentration range, i.e., responders; (b) low response to only the highest antigen concentrations; and (c) no response at any antigen concentration. Frequency distribution analysis of these groups indicated that a significant association occurred between the ability to respond and HL-A 5.
Subject(s)
Antigens, Bacterial , HLA Antigens , Histocompatibility Antigens , Lymphocytes/immunology , Streptodornase and Streptokinase/immunology , Adult , Aged , Humans , Immunogenetics , Lymphocyte Activation , Lymphocytes/metabolism , Middle Aged , Streptococcus/immunology , Thymidine/metabolism , TritiumABSTRACT
BACKGROUND: Trastuzumab-based adjuvant therapy has become the standard of care for human epidermal growth factor receptor-2 (HER2)-positive early breast cancer (EBC). Both anthracycline- and non-anthracycline-containing trastuzumab regimens are approved in the United States, but cardiotoxicity is increased with anthracycline-containing regimens. DESIGN: This paper reviews published and reported efficacy and cardiac safety data from the adjuvant trastuzumab trials [National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31/North Central Cancer Treatment Group (NCCTG) N9831, Breast Cancer International Research Group (BCIRG) 006, Herceptin Adjuvant (HERA), FinHer, and Programme Adjuvant Cancer Sein (PACS) 04]. RESULTS: The addition of trastuzumab to adjuvant chemotherapy significantly improved disease-free survival (from 24% to 58%) in five of the six trials. Overall survival was significantly improved (23%-35%) in the large trials. In NSABP B-31/ NCCTG N9831, 5.0%-6.6% of patients who received doxorubicin and cyclophosphamide (AC) were unable to receive trastuzumab. Cardiac event rate was highest in the anthracycline-containing trastuzumab arms (1.9%-3.8%) and lowest with the regimen of docetaxel, carboplatin, and trastuzumab (TCH) (0.4%). CONCLUSIONS: Incorporation of trastuzumab into anthracycline and non-anthracycline adjuvant chemotherapy regimens has substantially improved outcomes in HER2-postive EBC. The TCH regimen has the lowest rates of cardiac dysfunction, but uncertainty exists regarding the relative efficacy of TCH compared with anthracycline-containing trastuzumab regimens. Cardiac risk factor assessment can aid in selection of trastuzumab-based adjuvant therapy regimens.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Heart Diseases/prevention & control , Receptor, ErbB-2/metabolism , Antibodies, Monoclonal, Humanized , Chemotherapy, Adjuvant , Female , Heart Diseases/chemically induced , Humans , Outcome Assessment, Health Care , TrastuzumabABSTRACT
Predictive testing for Huntington disease (HD), by means of direct mutation analysis, has been offered at the Division of Human Genetics, University of Cape Town, from 1995. The aim of this study was to compile a comprehensive profile of the participants who had undergone predictive testing in the Western Cape from 1995 to 2005. The sociodemographic data, uptake and outcome of tests were analyzed to inform changes to improve the current genetic counseling services. A retrospective cross-sectional design using a 'multi-method' approach of both qualitative and quantitative methods was used. Data were gathered from the participants' hospital files and genetic database. Psychosocial data were obtained by face-to-face interviews with the participants in their homes or venues of choice. A total of 36 predictive tests were performed. The uptake for predictive testing was approximately 4.5% of the estimated at-risk population. The cohort of 27 individuals comprised 16 females and 11 males. Their mean age was 35.3 years; 6 were mixed ancestry and 21 were White people (European ancestry); 11 tested gene positive, 15 gene negative and 1 was in the reduced penetrance range. The most important issue identified was that the uptake of individuals classified as mixed ancestry was substantially lower than that of the White people possibly due to limited access to the predictive testing program because of the low levels of income and education in the general population of families with HD. Strategies to address these aspects have been incorporated into the program and will be reassessed after 1 year.
Subject(s)
Developing Countries , Genetic Testing/statistics & numerical data , Huntington Disease/diagnosis , Huntington Disease/genetics , Adult , Attitude to Health , Cohort Studies , Female , Genetic Counseling , Genetic Testing/psychology , Health Services Accessibility , Humans , Huntington Disease/psychology , Male , Middle Aged , Predictive Value of Tests , White People , Young AdultABSTRACT
The primitively social sweat bee, Lasioglossum zephyrum, blocks the entry into its nest of most conspecifics from other colonies. Laboratory inbreeding of these bees produced lines which showed a positive linear relationship between the coefficient of relationship of bees tested and how often they permitted non-nestmates to pass them. The most probable mechanism is a genetically determined odor coupled with a learned component by which guard bees discriminate between odors of close kin and other bees.
ABSTRACT
The density but not the affinity of beta-adrenergic receptors declined significantly with age in rat pineal gland, corpus striatum, and cerebellum, as determined by the binding of tritiated dihydroalprenolol. Exposing rats to light for 12 hours increased the binding of this radioligand in 3-month-old but not in 24-month-old rats. The reduced responsiveness to catecholamines seen in aging may be due to a decrease in the number of beta-adrenergic receptors which, in turn, may be caused by an impaired capacity of receptors in aged animals to adapt to changes in adrenergic neuronal input.
Subject(s)
Aging , Brain/metabolism , Pineal Gland/metabolism , Receptors, Adrenergic, beta/metabolism , Receptors, Adrenergic/metabolism , Alprenolol/analogs & derivatives , Alprenolol/metabolism , Animals , Cerebellum/metabolism , Circadian Rhythm , Corpus Striatum/metabolism , Kinetics , Light , Male , Neuroglia/metabolism , RatsABSTRACT
With the increase in uptake of multi-month antiretroviral therapy dispensing (MMD) for children, little is known about consistency of MMD receipt over time and its association with virological outcomes. This analysis aims to assess the uptake of 3-month MMD among children, consistent receipt of MMD after uptake, and clinical outcomes following transition to MMD in 16 health facilities in Gaza and Inhambane Provinces. This is a secondary analysis involving children <15 years living with HIV with clinical visits during the period from September 2019 to August 2020. Of 4383 children, 82% ever received MMD (at least one pickup of a 3-month MMD supply) during the study period but only 40% received it consistently (defined as MMD at every visit during the study period). Consistent MMD was most common among older children and children without indications of clinical instability. Overall viral load (VL) coverage was 40% (733/1851). Consistent MMD was significantly associated with lower odds of having a VL (0.78, 95% CI: 0.64-0.95). In conclusion, while receipt of a multi-month supply was common particularly during the early days of the COVID-19 pandemic, only a minority of children received consistent MMD; however, there is a need to ensure children with fewer visits still receive timely VL monitoring.
Subject(s)
Humans , Male , Female , Pregnancy , Child , Adolescent , Adult , Aged , Aged, 80 and over , HIV/drug effects , Art , MozambiqueABSTRACT
21 patients with chronic active hapatitis (CAH) and their families were HL-A typed. HL-A8 was significantly increased in frequency. An apparent increased frequency of HL-A1 was shown to be secondary to the increased HL-A8 due to linkage disequilibrium. Genotype analysis revealed a striking increased frequency of homozygosity for HL-A8, 6 of 21 patients (28.5%) vs. 2.8% of controls. Two patients and one normal who were homozygous for both HL-A1 and HL-A8 were found to be homozygous for a mixed lymphocyte culture (MLC) determinant 8a. Homozygous 8a cells were used as test-stimulating cells in one-way MLC reactions to determine the frequency of the expression of the 8a determinant in 17 patients and 49 controls selected for HL-A type. 8a was found to be associated with 50% of HL-A8 haplotypes and was frequent in the patient and control populations of the same HL-A types. These data suggest that susceptibility to CAH is determined by homozygosity for a gene that is in linkage disequilibrium with HL-A8 and more closely associated with the HL-A second locus then with the locus for the major MLC determinant.
Subject(s)
Hepatitis/genetics , Adolescent , Adult , Alleles , Child , Chromosome Mapping , Chronic Disease , Female , Genotype , HLA Antigens/analysis , Hepatitis/immunology , Humans , Lymphocyte Culture Test, Mixed , MaleABSTRACT
We have histocompatibility (HLA) genotyped 28 families with insulin-dependent diabetics in two or more consecutive generations, usually parent and child. This strategy of ascertainment was used to maximize the likelihood of obtaining a homogeneous type of disease within a family, and an autosomal dominant mode of inheritance. 76 diabetics and 169 nondiabetics were studied in these families. The frequencies of the antigens Dw3 and Dw4, and the genotype Dw3/Dw4 among the diabetics are 59, 68, and 30%, respectively, as compared with 15, 12, and 2% in normal controls, and 43, 41, and 10% in the nondiabetic relatives of the diabetics. Dw2 is present in only one diabetic (4%), as compared with 18% in normal controls and 17% in nondiabetic relatives.HLA haplotype concordance was analyzed for sib pairs in relation to the haplotype shared by the affected parent/child pair, and for the diabetic sib pairs within each sibship. The results failed to reveal deviations in the expected HLA haplotype assortment. Assuming an autosomal dominant mode and several penetrance levels, linkage analysis between the HLA and diabetes was performed. The total lod score is 0.37 for a recombination fraction of 0.29 at 50% penetrance. Although the linkage and concordance analysis results are inconclusive, they seem to be different from those reported by us for families with normal parents and two or more diabetic sibs. Because ascertainment biases may have influenced these results in an unquantifiable manner, it is not certain whether the two types of families are genetically different. However, the marked difference in the lod scores for the 50% penetrant autosomal recessive model between the two types of families is compatible with a genetic dissimilarity between them. The high frequency of the Dw3 and Dw4 antigens, the Dw3/Dw4 genotype, and the decreased frequency of Dw2, however, indicate the existence of two or more important diabetic genetic factors associated with the D region of the HLA in these families.
Subject(s)
Diabetes Mellitus, Type 1/genetics , HLA Antigens/genetics , Diabetes Mellitus, Type 1/immunology , Female , Genes, Dominant , Genes, MHC Class II , Genetic Linkage , Humans , Male , Models, Genetic , Pedigree , Statistics as TopicABSTRACT
The Argentine ant, Linepithema humile (Mayr), and the red imported fire ant, Solenopsis invicta Buren, are natural agonists in their country of origin. Since the first report of L. humile in California in 1907 its range expanded statewide, displacing native ant species wherever it spread. Since the discovery of established populations of S. invicta in southern California in 1998, it has been restricted to discrete areas of southern California. However, as these discrete populations expand, they are encountering large populations of L. humile, which are effective competitors for available resources and are particularly aggressive in their encounters with other ant species such as S. invicta. Most Dolichoderine ants such as L. humile do not prefer to forage on baits made with defatted corn grit and soybean oil typically used in red imported fire ant control programs. Applications of these baits in areas where distributions of these species overlap might selectively affect populations of S. invicta and give L. humile a competitive advantage. Three laboratory experiments were conducted to determine the competitive outcomes between S. invicta pitted against L. humile: 1) agonistic behavior of workers in small arenas, 2) colony interactions with different population ratios, and 3) the effects of pyriproxyfen on the competitiveness of S. invicta against L. humile. Populations of S. invicta consisting of major workers killed more L. humile than did minors or a mixture of majors and minors. When paired against L. humile colonies consisting of 1,100 workers, colonies consisting of 38 S. invicta workers were easily defeated by L. humile. Colonies consisting of 450 S. invicta workers plugged their nest entrances, but they were ultimately defeated by L. humile after 13 d. The S. invicta colonies consisting of 1,100 workers took control of the bridge connecting the colonies, invaded the L. humile colony, killed the Argentine ant queens, and removed their brood. Pyriproxyfen-treated fire ant workers took significantly longer to chase the Argentine ants from a connecting bridge than did untreated fire ants. Thus, fire ant baits may have long-term effects on intercolonial aggression between S. invicta and L. humile, especially when Argentine ant populations are high in the summer.
Subject(s)
Aggression/physiology , Ants/physiology , Behavior, Animal/physiology , Animals , Ants/drug effects , Insecticides/pharmacology , Pyridines/pharmacologyABSTRACT
Essential criteria for the methodological quality and validity of randomized controlled trials are the drop-out rates from both the experimental intervention and the study as a whole. This systematic review and meta-analysis assessed these drop-out rates in non-pharmacological schizophrenia trials. A systematic literature search was used to identify relevant trials with ≥100 sample size and to extract the drop-out data. The rates of drop-out from the experimental intervention and study were calculated with meta-analysis of proportions. Meta-regression was applied to explore the association between the study and sample characteristics and the drop-out rates. 43 RCTs were found, with drop-out from intervention ranging from 0% to 63% and study drop-out ranging from 4% to 71%. Meta-analyses of proportions showed an overall drop-out rate of 14% (95% CI: 13-15%) at the experimental intervention level and 20% (95% CI: 17-24%) at the study level. Meta-regression showed that the active intervention drop-out rates were predicted by the number of intervention sessions. In non-pharmacological schizophrenia trials, drop-out rates of less than 20% can be achieved for both the study and the experimental intervention. A high heterogeneity of drop-out rates across studies shows that even lower rates are achievable.
Subject(s)
Antipyretics/therapeutic use , Data Collection/statistics & numerical data , Randomized Controlled Trials as Topic/methods , Schizophrenia/therapy , Humans , Patient Dropouts/statistics & numerical dataABSTRACT
BACKGROUND: To date, 43 types of Spinocerebellar Ataxias (SCAs) have been identified. A subset of the SCAs are caused by the pathogenic expansion of a CAG repeat tract within the corresponding gene. Ethnic and geographic differences are evident in the prevalence of the autosomal dominant SCAs. Few descriptions of the clinical phenotype and molecular genetics of the SCAs are available from the African continent. Established studies mostly concern the South African populations, where there is a high frequency of SCA1, SCA2 and SCA7. The SCA7 mutation in South Africa (SA) has been found almost exclusively in families of indigenous Black African ethnic origin. OBJECTIVE: To present the results of the first clinical description of seven Zambian families presenting with autosomal dominant SCA, as well as the downstream molecular genetic analysis of a subset of these families. METHODS: The study was undertaken at the University Teaching Hospital in Lusaka, Zambia. Ataxia was quantified with the Brief Ataxia Rating Scale derived from the modified international ataxia rating scale. Molecular genetic testing for 5 types of SCA (SCA1, SCA2, SCA3, SCA6 and SCA7) was performed at the National Health Laboratory Service at Groote Schuur Hospital and the Division of Human Genetics, University of Cape Town, SA. The clinical and radiological features were evaluated in seven families with autosomal dominant cerebellar ataxia. Molecular genetic analysis was completed on individuals representing three of the seven families. RESULTS: All affected families were ethnic Zambians from various tribes, originating from three different regions of the country (Eastern, Western and Central province). Thirty-four individuals from four families had phenotypic features of SCA7. SCA7 was confirmed by molecular testing in 10 individuals from 3 of these families. The age of onset of the disease varied from 12 to 59 years. The most prominent phenotypic features in these families were gait and limb ataxia, dysarthria, visual loss, ptosis, ophthalmoparesis/ophthalmoplegia, pyramidal tract signs, and dementia. Affected members of the SCA7 families had progressive macular degeneration and cerebellar atrophy. All families displayed marked anticipation of age at onset and rate of symptom progression. The pathogenic SCA7 CAG repeat ranges varied from 47 to 56 repeats. Three additional families were found to have clinical phenotypes associated with autosomal dominant SCA, however, DNA was not available for molecular confirmation. The age of onset of the disease in these families varied from 19 to 53 years. The most common clinical picture in these families included a combination of cerebellar symptoms with slow saccadic eye movements, peripheral neuropathy, dementia and tremor. CONCLUSION: SCA is prevalent in ethnic Zambian families. The SCA7 families in this report had similar clinical presentations to families described in other African countries. In all families, the disease had an autosomal dominant pattern of inheritance across multiple generations. All families displayed anticipation of both age of onset and the rate of disease progression. Further clinical and molecular investigations of the inherited ataxias in a larger cohort of patients is important to understand the natural history and origin of SCAs in the Zambian population.
ABSTRACT
Mice homozygous for the mutation "nude" (nu/nu) are athymic and lack thymus-dependent lymphocytes. Heterozygote (nu/+) controls, which are phenotypically and immunologically normal, and (nu/nu) mice were infected with 1.0 times 10-6 colony-forming units of Phipps strain BCG. In the spleens of nu/+ mice, there was a progressive increase in number of BCG up to the second week, followed by a gradual decline. However, in the nu/nu mice, BCG growth was gradual and continuous until termination of the experiment at 5 weeks. In the lung, significant differences were not noted until after the second week, at which time the nude mice showed a rapid increase (of more than 2 log10) in the number of BCG. However, the number of BCG was not significantly greater in the livers of either group. Changes in the normal histology of the lung included a massive influx of monocytes during the first 2 weeks which peaked at day 21. In the lungs of the nu/+ mice by day 28, there was considerable granuloma formation consisting of monocytes and small lymphocytes. However, in the lungs of nu/nu animals, the granulomas were made up primarily of monocytes with a lack of small lymphocytes. Acid-fast stains confirmed the presence of large numbers of organisms in the macrophages of nu/nu mice, with gradual destruction of these phagocytic cells.