Laetoli's lost tracks: 3D generated mean shape and missing footprints.

The Laetoli site (Tanzania) contains the oldest known hominin footprints, and their interpretation remains open to debate, despite over 35 years of research. The two hominin trackways present are parallel to one another, one of which is a composite formed by at least two individuals walking in single file. Most researchers have focused on the single, clearly discernible G1 trackway while the G2/3 trackway has been largely dismissed due to its composite nature. Here we report the use of a new technique that allows us to decouple the G2 and G3 tracks for the first time. In so doing we are able to quantify the mean footprint topology of the G3 trackway and render it useable for subsequent data analyses. By restoring the effectively 'lost' G3 track, we have doubled the available data on some of the rarest traces directly associated with our Pliocene ancestors.

Does footprint depth correlate with foot motion and pressure?

Footprints are the most direct source of evidence about locomotor biomechanics in extinct vertebrates. One of the principal suppositions underpinning biomechanical inferences is that footprint geometry correlates with dynamic foot pressure, which, in turn, is linked with overall limb motion of the trackmaker. In this study, we perform the first quantitative test of this long-standing assumption, using topological statistical analysis of plantar pressures and experimental and computer-simulated footprints. In computer-simulated footprints, the relative distribution of depth differed from the distribution of both peak and pressure impulse in all simulations. Analysis of footprint samples with common loading inputs and similar depths reveals that only shallow footprints lack significant topological differences between depth and pressure distributions. Topological comparison of plantar pressures and experimental beach footprints demonstrates that geometry is highly dependent on overall print depth; deeper footprints are characterized by greater relative forefoot, and particularly toe, depth than shallow footprints. The highlighted difference between 'shallow' and 'deep' footprints clearly emphasizes the need to understand variation in foot mechanics across different degrees of substrate compliance. Overall, our results indicate that extreme caution is required when applying the 'depth equals pressure' paradigm to hominin footprints, and by extension, those of other extant and extinct tetrapods.

Molecular typing of Treponema pallidum strains from patients with neurosyphilis in Pretoria, South Africa.

OBJECTIVE: To evaluate the molecular typing system for Treponema pallidum using cerebrospinal fluid (CSF) specimens obtained from patients with neurosyphilis in Pretoria, South Africa. METHODS: CSF specimens were collected from 32 men and 18 women with suspected late neurosyphilis. Typing of T pallidum involved PCR amplification and restriction analysis of the tprE, G and J genes and determination of the number of 60 base pair tandem repeats within the arp gene by PCR amplification. RESULTS: Of 13 typeable specimens, 4 strain types were identified: 2i, 3e, 14a and 17e. Subtype 14a was identified in 7 specimens (53.8%), subtype 3e in 4 specimens (30.7%) and subtypes 17e and 2i in 1 specimen (7.6%) each. CONCLUSIONS: This study shows that the typing system can be applied to specimens which may contain low numbers of spirochaetes such as CSF.

Increasing relative prevalence of HSV-2 infection among men with genital ulcers from a mining community in South Africa.

OBJECTIVES: To determine the aetiology of genital ulcer disease (GUD) and its association with HIV infection in the mining community of Carletonville, South Africa, from two cross sectional surveys of consecutive men presenting with genital lesions during October 1993 to January 1994 and July to November 1998. METHODS: A multiplex polymerase chain reaction (M-PCR) assay combined with amplicon detection was used to identify DNA specific sequences of Treponema pallidum, herpes simplex virus (HSV), and Haemophilus ducreyi. A real time PCR assay was used to differentiate between HSV-1 and HSV-2. RESULTS: M-PCR detected T pallidum, HSV, and H ducreyi in 10.3%, 17.2%, and 69.4% of 232 GUD patients during 1993-4 and in 12.4%, 36.0%, and 50.5% of 186 GUD patients in 1998. The proportion of patients with more than one agent increased significantly from 7.3% (17/232) in 1993-4 to 16.7% (31/186) in 1998 (p <0.01). HSV-2 was detected in a higher proportion of ulcer specimens from HIV infected patients than in specimens from HIV uninfected patients during both time periods (1993-4: 26.2% v 6.7%, p <0.001; 1998: 42.1% v 29.6%, p >0.09). CONCLUSIONS: Based on two cross sectional surveys, 4 years apart, chancroid remained the leading cause of GUD in men who presented at the STD clinic with genital ulcers in the mining community of Carletonville, South Africa. The relative prevalence of primary syphilis has remained low. However, HSV-2 has emerged as a more significant cause of GUD and the proportion of GUD patients infected with more than one agent also increased significantly. HSV-2 DNA was detected in a significantly higher proportion of ulcer specimens from HIV positive patients than from HIV negative patients. No association was found between HIV infection status and the relative prevalence of chancroid or syphilis.

Molecular typing of Treponema pallidum in South Africa: cross-sectional studies.

We evaluated a molecular subtyping system for Treponema pallidum for its ability to differentiate between strains obtained from male patients with primary syphilis in South Africa. Of 201 T. pallidum-positive specimens, 161 were typeable, revealing 35 subtypes. The unique subtypes identified in Durban, Cape Town, and Carletonville and the total number of subtypes suggested that the strain population was very diverse and varied geographically.

Acid-base balance and nutrition in peritoneal dialysis.

Acidosis has been implicated in increased protein catabolism and malnutrition of dialysis. The present study examines the effect of acid-base balance on the nutrition status of peritoneal dialysis (PD) patients. We followed 43 PD patients for one year. Blood chemistries were measured monthly. Patients were divided on the basis of subjective global assessment (SGA) into well-nourished (A), mildly-to-moderately malnourished (B), and severely malnourished (C) groups. Mean serum bicarbonate and albumin concentrations were, for group A (n = 16), 23.5 mmol/L and 3.96 g/dL respectively; for group B (n = 17), 27.2 mmol/L and 3.50 g/dL respectively; and for group C (n = 10), 25.9 mmol/L and 2.9 g/dL respectively. In group A, mean serum bicarbonate was significantly lower, and albumin concentration significantly higher as compared with the other groups. Interestingly, of 9 patients with serum HCO3 < 22 mmol/L, 6 were in group A and 2 were in group B. Of 6 patients with serum HCO3 > 29 mmol/L, 5 were in group B and 4 were in group C. The data suggest that well-nourished PD patients tend to be more acidotic. Malnutrition in alkalotic PD patients may be due to low protein intake resulting in decreased acid production; however, an effect of alkalosis on protein metabolism cannot be excluded.

Identification and characterization of a high-affinity zinc uptake system in Neisseria gonorrhoeae.

A search of the gonococcal genome database using the known zinc-binding protein (znuA) sequences from Escherichia coli and Haemophilus influenzae identified an open reading frame encoding a putative gonococcal ZnuA. The consensus amino acid sequence of this open reading frame possessed a characteristic 30-amino acid histidine-rich metal-binding motif (repetitive HDH sequence) containing 43% histidine and 37% aspartic acid and glutamic acid. Subsequently, two adjacent open reading frames with homology to E. coli and H. influenzae znuB and znuC were located upstream of znuA. When partially purified from sonicated cell-free supernatants by CM-Sepharose chromatography, the mature gonococcal ZnuA had an estimated molecular mass of 38 kDa by SDS-PAGE. The presence of a DNA sequence encoding a 19-amino acid signal peptide and the solubility of the mature ZnuA suggested that this protein was located in the periplasm. Inactivation of the Neisseria gonorrhoeae F62 znuA by insertional mutagenesis resulted in a mutant that had a growth rate lower than that of the wild-type parent strain and that required high concentrations of ZnCl2 (> or = 200 microM) for optimal growth. Using a chemically defined agar medium, the gonococcal ZnuA mutant grew only in the presence of Zn(2+), whereas Mg(2+), Ca(2+), Ni(2+), Fe(2+), Cu(2+), Mn(2+) and Cd(2+) had either no effect or were growth inhibitory.

New tests for bacterial sexually transmitted diseases.

Recent advances in diagnostic tests for sexually transmitted diseases include the development of a synthetic Venereal Disease Research Laboratory reagent that will improve the sensitivity and stability of nontreponemal serologic tests for syphilis. A second generation user friendly and high throughput nucleic acid amplification test for Chlamydia trachomatis and Neisseria gonorrhoeae has also been developed.

Recovery of memory function following traumatic brain injury in pre-school children.

Traumatic brain injury (TBI) may have a profound impact on a child's ongoing development. Various risk factors have been found to predict outcome, but considerable variability remains unexplained. This study used a prospective, longitudinal design to examine recovery of memory function following TBI within the pre school period. Ninety-six children with TBI were divided according to injury severity (mild, moderate, severe), and compared to age and SES matched healthy controls (n = 35). Children were evaluated acutely and at 6,12 and 18 months post-injury using intellectual and memory measures. Results showed a relationship between greater injury severity and poorer intellectual ability. This dose-response relationship was not clearly evident for memory function within the acute phase of recovery, but developed over time, with greater memory impairments evident for children with more severe TBI by 12 months post-injury. Children with mild TBI exhibited few memory problems. Findings are discussed in the context of theories of plasticity and recovery of function.

Human immunodeficiency virus infection and genital ulcer disease in South Africa: the herpetic connection.

BACKGROUND AND OBJECTIVES: While genital ulcers are a risk factor in HIV infection, the association of specific agents of genital ulcer disease (GUD) with HIV infection may vary. GOAL: To determine the etiology of GUD in HIV-infected and HIV-uninfected men attending sexually transmitted disease (STD) clinics in Durban, Johannesburg, and Cape Town, South Africa, and the association of previous and current sexually transmitted infections with HIV infection in men with ulcerative and nonulcerative STDs. STUDY DESIGN: A cross-sectional study of 558 men with genital ulcers and 602 men with urethritis. RESULTS: Patients with GUD were more likely to be infected with HIV than patients with urethritis (39.4% versus 21.4%, P< or =0.001). Herpes simplex virus 2 (HSV-2) was the most common agent identified in ulcer specimens (35.9%), and was detected in a significantly higher proportion of ulcer specimens from HIV-infected patients than in specimens from HIV-uninfected patients (47.4% versus 28.2%, P< or =0.001). Patients infected with HIV-1 were significantly more likely to have HSV-2 infection, as measured by the presence of the antibody to glycoprotein G-2, than patients not infected with HIV (63.1% versus 38.5%, P< or =0.001). Patients infected with HIV-1 were also significantly more likely to have initial HSV-2 infection than HIV-uninfected patients with GUD (50.0% versus 31.6%, P = 0.007). Haemophilus ducreyi was detected in 31.7% of ulcer specimens; prevalence did not vary by HIV-infection status. Treponema pallidum DNA was detected significantly less frequently in ulcer specimens from patients infected with HIV than in specimens from patients not infected with HIV (10.2% versus 26%, P< or =0.001); no association was found between HIV-infection status and fluorescent treponemal antibody absorption test seroreactivity, even when men with M-PCR-positive syphilis lesions were excluded from the analyses. CONCLUSION: The authors found that HSV-2 is a more common etiology of GUD than has been suggested by previous studies conducted in South Africa; serologic evidence of HSV-2 infection and current cases of genital herpes are strongly associated with HIV infection among men who present to STD clinics with GUD or urethritis.

Etiology of genital ulcer disease in Dakar, Senegal, and comparison of PCR and serologic assays for detection of Haemophilus ducreyi.

We used PCR assays to determine the etiology of genital ulcers in patients presenting to a sexually transmitted disease clinic in Dakar, Senegal, and evaluated the ability of two PCR tests (groEL and recD) and two serological tests (adsorption enzyme immunoassay [EIA] and lipooligosaccharide [LOS] EIA) to detect current Haemophilus ducreyi infection. We found that in this population, H. ducreyi, T. pallidum, and herpes simplex virus HSV DNA were detected in 56, 15, and 13% of 39 genital ulcer specimens, respectively, and H. ducreyi DNA was detected in 60% (3 of 5) of samples from ulcerated bubos. Among 40 consecutive patients with genital ulcer disease and with sufficient sample for both PCR assays, the recD and groEL H. ducreyi PCR assays were 83% concordant, with the recD PCR assay detecting six (15%) additional positive specimens and the groEL assay detecting one (3%) additional positive specimen. Compared to PCR, the adsorption EIA and LOS EIA tests had sensitivities of 71 and 59% and specificities of 57 and 90%, respectively, for the diagnosis of current H. ducreyi infection. While these differences in specificity could be due either to previous infection with H. ducreyi or to the detection of cross-reacting antibodies, only 6% of patients from a nearby family planning clinic gave a positive reaction in both the adsorption EIA and LOS EIA assays, indicating that cross-reacting antibodies are not prevalent among clinic attendees in this city. Our studies indicate that the adsorption EIA detects both current and past infection, while the LOS EIA assay is more specific for current infection with H. ducreyi in this population.

Neisseria gonorrhoeae bacterioferritin: structural heterogeneity, involvement in iron storage and protection against oxidative stress.

The iron-storage protein bacterioferritin (Bfr) from Neisseria gonorrhoeae strain F62 was identified in cell-free extracts and subsequently purified by column chromatography. Gonococcal Bfr had an estimated molecular mass of 400 kDa by gel filtration; however, analysis by SDS-PAGE revealed that it was composed of 18 kDa (BfrA) and 22 kDa (BfrB) subunits. DNA encoding BfrB was amplified by PCR using degenerate primers derived from the N-terminal amino acid sequence of BfrB and from a C-terminal amino acid sequence of Escherichia coli Bfr. The DNA sequence of bfrA was subsequently obtained by genome walking using single-specific-primer PCR. The two Bfr genes were located in tandem with an intervening gap of 27 bp. A potential Fur-binding sequence (12 of 19 bp identical to the consensus neisserial fur sequence) was located within the 5' flanking region of bfrA in front of a putative -35 hexamer. The homology between the DNA sequences of bfrA and bfrB was 55.7%; the deduced amino acid sequences of BfrA (154 residues) and BfrB (157 residues) showed 39.7% identity, and showed 41.3% and 56.1% identity, respectively, to E. coli Bfr. Expression of recombinant BfrA and BfrB in E. coli strain DH5alpha was detected on Western blots probed with polyclonal anti-E. coli Bfr antiserum. Most Bfrs are homopolymers with identical subunits; however, the evidence presented here suggests that gonococcal Bfr was composed of two similar but not identical subunits, both of which appear to be required for the formation of a functional Bfr. A Bfr-deficient mutant was constructed by inserting the omega fragment into the BfrB gene. The growth of the BfrB-deficient mutant in complex medium was reduced under iron-limited conditions. The BfrB-deficient mutant was also more sensitive to killing by H2O2 and paraquat than the isogenic parent strain. These results demonstrate that gonococcal Bfr plays an important role in iron storage and protection from iron-mediated oxidative stress.

Chancroid, primary syphilis, genital herpes, and lymphogranuloma venereum in Antananarivo, Madagascar.

Ulcer material from consecutive patients attending clinics in Antananarivo, Madagascar, was tested using multiplex polymerase chain reaction (M-PCR) to detect Treponema pallidum, Haemophilus ducreyi, and herpes simplex virus. Sera were tested for syphilis and for IgG and IgM antibodies to Chlamydia trachomatis by microimmunofluorescence testing (MIF). By M-PCR, 33% of 196 patients had chancroid, 29% had syphilitic ulcers, and 10% had genital herpes; 32% of the ulcer specimens were M-PCR negative. Compared with M-PCR, syphilis serology was 72% sensitive and 83% specific. The sensitivity of clinical diagnosis of syphilis, chancroid, and genital herpes was 93%, 53%, and 0% and specificity was 20%, 52%, and 99%, respectively. Less schooling was associated with increased prevalence of syphilitic ulcers (P=.001). Sixteen patients (8%) were clinically diagnosed with lymphogranuloma venereum (LGV); 1 plausible case of LGV was found by MIF. In Madagascar, primary care of genital ulcers should include syndromic treatment for syphilis and chancroid.

HIV-1 and other sexually transmitted infections in a cohort of female sex workers in Chiang Rai, Thailand.

OBJECTIVES: To determine demographic and behavioural factors and sexually transmitted infections (STIs) associated with prevalent HIV-1 infection among brothel based and other female sex workers (FSWs) in Chiang Rai, northern Thailand. METHODS: Data were collected from questionnaires, physical examinations, and laboratory evaluations on Thai FSWs enrolled in a prospective cohort study in Chiang Rai, Thailand, from 1991 to the end of 1994. RESULTS: HIV-1 seroprevalence was 32% among 500 women: 47% for 280 brothel workers and 13% for 220 other FSWs (p < 0.001); 96% of infections were due to HIV-1 subtype E. At enrolment, other STIs were common: chlamydia, 20%; gonorrhoea, 15%; active syphilis (serological diagnosis), 9%; genital ulcer, 12%; seroreactivity to Haemophilus ducreyi, 21%, and herpes simplex virus type 2 (HSV-2), 76%. On multiple logistic regression analysis, HIV-1 was associated with brothel work, birth in upper northern Thailand, initiation of commercial sex at < 15 years of age, syphilis, HSV-2 seropositivity, and genital ulcer. CONCLUSIONS: Young Thai FSWs working in brothels in northern Thailand in the early phase of the HIV epidemic have been at very high risk for HIV-1 infection and several other STIs. Programmes are needed to prevent girls and young women from entering the sex industry and to reduce the risk of infection with HIV-1 and other STIs.

Genital ulcers: etiology, clinical diagnosis, and associated human immunodeficiency virus infection in Kingston, Jamaica.

Individuals presenting consecutively with genital ulcers in Kingston, Jamaica, underwent serological testing for human immunodeficiency virus (HIV) infection, chlamydial infection, and syphilis. Ulcer material was analyzed by multiplex polymerase chain reaction (M-PCR) analysis. DNA from herpes simplex virus (HSV), Haemophilus ducreyi, and Treponema pallidum was detected in 158 (52.0%), 72 (23.7%), and 31 (10.2%) of 304 ulcer specimens. Of the 304 subjects, 67 (22%) were HIV-seropositive and 64 (21%) were T. pallidum-seroreactive. Granuloma inguinale was clinically diagnosed in nine (13.4%) of 67 ulcers negative by M-PCR analysis and in 12 (5.1%) of 237 ulcers positive by M-PCR analysis (P = .03). Lymphogranuloma venereum was clinically diagnosed in eight patients. Compared with M-PCR analysis, the sensitivity and specificity of a clinical diagnosis of syphilis, herpes, and chancroid were 67.7%, 53.8%, and 75% and 91.2%, 83.6%, and 75.4%, respectively. Reactive syphilis serology was 74% sensitive and 85% specific compared with M-PCR analysis. Reported contact with a prostitute in the preceding 3 months was associated with chancroid (P = .009), reactive syphilis serology (P = .011), and HIV infection (P = .007). The relatively poor accuracy of clinical and locally available laboratory diagnoses pleads for syndromic management of genital ulcers in Jamaica. Prevention efforts should be intensified.

Molecular characterization of Haemophilus ducreyi strains from Jackson, Mississippi, and New Orleans, Louisiana.

Chancroid, a sexually transmitted disease caused by Haemophilus ducreyi, is one of the most common genital ulcer diseases in developing countries. In the United States, while less common, the disease has been associated with outbreaks in inner cities, particularly among persons who engage in sex for drugs or money. Two outbreaks of chancroid were recently studied in the United States, one in New Orleans (from 1990 to 1992) and one in Jackson, Mississippi (from 1994 to 1995). By use of ribotyping, plasmid content, and antibiotic susceptibility, the chancroid cases in New Orleans were found to be due to a limited number of strains, consistent with a limited introduction of H. ducreyi into this community. The H. ducreyi isolates from New Orleans and Jackson had different ribotype patterns, suggesting that the two outbreaks were probably not linked.

Functional memory skills following traumatic brain injury in young children.

Traumatic brain injury (TBI) may have a profound impact on a child's ongoing development. Various risk factors have been found to predict outcome, but considerable variability remains unexplained. This study used a prospective, longitudinal design to examine recovery of memory function following TBI within the pre-school period. Forty-four children with TBI were divided according to injury severity (mild, moderate, severe), and compared to age and SES matched healthy controls (n = 26). Children were evaluated acutely and at 12 months post-injury using the Rivermead Behavioural Memory Test for Children. Results failed to show a clear dose-response relationship between injury severity and memory function during the acute phase of recovery. However, this relationship developed over time, with greater memory impairments evident for children with more severe TBI by 12 months post-injury. Children with mild TBI exhibited few memory problems.