The foot of Homo naledi.

Modern humans are characterized by a highly specialized foot that reflects our obligate bipedalism. Our understanding of hominin foot evolution is, although, hindered by a paucity of well-associated remains. Here we describe the foot of Homo naledi from Dinaledi Chamber, South Africa, using 107 pedal elements, including one nearly-complete adult foot. The H. naledi foot is predominantly modern human-like in morphology and inferred function, with an adducted hallux, an elongated tarsus, and derived ankle and calcaneocuboid joints. In combination, these features indicate a foot well adapted for striding bipedalism. However, the H. naledi foot differs from modern humans in having more curved proximal pedal phalanges, and features suggestive of a reduced medial longitudinal arch. Within the context of primitive features found elsewhere in the skeleton, these findings suggest a unique locomotor repertoire for H. naledi, thus providing further evidence of locomotor diversity within both the hominin clade and the genus Homo.

Midtarsal break variation in modern humans: Functional causes, skeletal correlates, and paleontological implications.

The midtarsal break was once treated as a dichotomous, non-overlapping trait present in the foot of non-human primates and absent in humans. Recent work indicates that there is considerable variation in human midfoot dorsiflexion, with some overlap with the ape foot. These findings have called into question the uniqueness of the human lateral midfoot, and the use of osteological features in fossil hominins to characterize the midfoot of our extinct ancestors. Here, we present data on plantar pressure and pedal mechanics in a large sample of adults and children (n = 671) to test functional hypotheses concerning variation in midfoot flexibility. Lateral midfoot peak plantar pressure correlates with both sagittal plane flexion at the lateral tarsometatarsal joint, and dorsiflexion at the hallucal metatarsophalangeal joint. The latter finding suggests that midfoot laxity may compromise hallucal propulsion. Multiple regression statistics indicate that a low arch and pronation of the foot explain 40% of variation in midfoot peak plantar pressure, independent of age and BMI. MRI scans on a small subset of study participants (n = 19) reveals that curvature of the base of the 4th metatarsal correlates with lateral midfoot plantar pressure and that specific anatomies of foot bones do indeed reflect relative midfoot flexibility. However, while the shape of the base of the 4th metatarsal may reliably reflect midfoot mobility in individual hominins, given the wide range of overlapping variation in midfoot flexibility in both apes and humans, we caution against generalizing foot function in extinct hominin species until larger fossils samples are available.

Solid State Multinuclear Magnetic Resonance Investigation of Electrolyte Decomposition Products on Lithium Ion Electrodes.

Solid electrolyte interphase (SEI) formation in lithium ion cells prepared with advanced electrolytes is investigated by solid state multinuclear (7Li, 19F, 31P) magnetic resonance (NMR) measurements of electrode materials harvested from cycled cells subjected to an accelerated aging protocol. The electrolyte composition is varied to include the addition of fluorinated carbonates and triphenyl phosphate (TPP, a flame retardant). In addition to species associated with LiPF6 decomposition, cathode NMR spectra are characterized by the presence of compounds originating from the TPP additive. Substantial amounts of LiF are observed in the anodes as well as compounds originating from the fluorinated carbonates.

The management of Clostridium difficile-associated diarrhoea in a community hospital.

OBJECTIVE: To review the management of patients with Clostridium difficile-associated diarrhoea (CDAD). METHODS: A retrospective study was conducted on 26 patients with clinical symptoms of CDAD and positive tests for C difficile toxins A and/or B in stool samples, over a 12- month period. Demographic and clinical data on the patients including use of proton pump inhibitors (PPI), management of CDAD, and compliance with local Infection Prevention and Control Guidelines were examined. RESULTS: The majority of patients were over 45 years of age (24/26, 92.4%) and 42% (11/26) were over 80 years of age. At least 50% (13/26) of the patients had acquired CDAD in hospital, 15% (4/26) were community acquired and symptomatic at admission while the onset of diarrhoea following admission to hospital was not documented in 35% (9/26). Three (11%) patients had used PPI. Fifteen per cent (4/26) of patients had no history of previous antibiotic therapy; 40% (10/26) were treated with a cephalosporin, fluoroquinolone or a combination of at least two different classes of antibiotics; one (3%) patient was on augmentin and the antibiotic regime used was not documented in 42% (11/26) who also had previous antibiotic therapy. The conditions for which antibiotics were prescribed could not be ascertained in 58% (15/26) but among the remaining cases antibiotics had been prescribed for urinary tract infection, wound respiratory tract infections and sepsis. Metronidazole (18/26, 70%) was the preferred drug of choice for first line therapy in patients with CDAD. None of the patients in the study received the recommended 10 to 14 days of antimicrobial therapy for CDAD. Recurrent CDAD was observed in 40% of those who were treated with metronidazole. The study also showed that there was timely reporting of laboratory results and good compliance with the hospital Infection Prevention and Control Guidelines. CONCLUSION: The findings of this study can be used as a process improvement measure in the management of patients with CDAD.

The management of Clostridium difficile-associated diarrhoea in a community hospital / Tratamiento de diarreas asociadas con Clostridium difficile en un hospital comunitario

OBJECTIVES: To review the management of patients with Clostridium difficile-associated diarrhoea (CDAD). METHODS: A retrospective study was conducted on 26 patients with clinical symptoms of CDAD and positive tests for C difficile toxins A and/or B in stool samples, over a 12- month period. Demographic and clinical data on the patients including use ofproton pump inhibitors (PPI), management of CDAD, and compliance with local Infection Prevention and Control Guidelines were examined. RESULTS: The majority ofpatients were over 45 years of age (24/26, 92.4%) and 42% (11/26) were over 80 years of age. At least 50% (13/26) of the patients had acquired CDAD in hospital, 15% (4/26) were community acquired and symptomatic at admission while the onset of diarrhoea following admission to hospital was not documented in 35% (9/26). Three (11%) patients had used PPI. Fifteen per cent (4/26) of patients had no history of previous antibiotic therapy; 40% (10/26) were treated with a cephalosporin, fluoroquinolone or a combination of at least two different classes of antibiotics; one (3%) patient was on augmentin and the antibiotic regime used was not documented in 42% (11/26) who also had previous antibiotic therapy. The conditions for which antibiotics were prescribed could not be ascertained in 58% (15/26) but among the remaining cases antibiotics had been prescribed for urinary tract infection, wound respiratory tract infections and sepsis. Metronidazole (18/26, 70%) was the preferred drug of choice for first line therapy in patients with CDAD. None of the patients in the study received the recommended 10 to 14 days of antimicrobial therapy for CDAD. Recurrent CDAD was observed in 40% of those who were treated with metronidazole. The study also showed that there was timely reporting oflaboratory results and good compliance with the hospital Infection Prevention and Control Guidelines. CONCLUSION: The findings of this study can be used as a process improvement measure in the management of patients with CDAD.

OBJETIVO: Revisar el tratamiento de pacientes con diarrea asociada con Clostridium difficile (DACD). MÉTODO: Se llevó a cabo un estudio retrospectivo de 26 pacientes aquejados por síntomas clínicos de DACD. Dichos pacientes resultaron positivos a pruebas de detección de toxinas A y/o B de C difficile en muestras de heces fecales por un período de 12 meses. Se examinaron los datos demográficos y clínicos de los pacientes, incluyendo el uso de inhibidores de la bomba de protones (IBP), tratamiento de la DACD, y el cumplimiento con las guías para el control de la infección local. RESULTADOS: La mayoría de los pacientes tenían más de 45 años de edad (24/26, 92.4%) y 42% (11/26) estaban por encima de los 80 años de edad. Al menos 50% (13/26) de los pacientes habían adquirido DACD en el hospital; el 15 % (4/26) la adquirió en la comunidad y presentaba síntomas al momento del ingreso; el comienzo de la diarrea tras el ingreso al hospital no se documentó en 35% (9/26) de los casos. Tres pacientes (11%) habían usado IBP. El 15% (4/26) de los pacientes no tenían antecedente alguno de terapia con antibióticos; un 40% (10/26) fue tratado con cefalosporina, fluoroquinolona, o una combinación por lo menos dos clases diferentes del antibióticos; un paciente (3%) se hallaba bajo tratamiento con augmentina y el régimen antibiótico usado no se documentó en el 42% (11/26) de los casos, que también tuvieron terapia antibiótica previa. No pudieron determinarse las condiciones para las que se prescribieron los antibióticos en el 58% (15/26), pero entre los casos restantes, se habían prescrito antibióticos para la infección de las vías urinarias, heridas, infecciones de las vías respiratorias, y sepsis. El metronidazol (18/26, 70%) fue el medicamento de opción preferida para la terapia de primera línea en los pacientes con DACD. Ninguno de los pacientes en el estudio recibió los 10 a 14 días de terapia antimicrobiana, recomendados para la DACD. Se observó DACD recurrente en 40% de aquéllos que fueron tratados con metronidazol. El estudio también mostró que hubo reportes oportunos de resultados de laboratorio y buen cumplimiento de las guías hospitalarias para el control de las infecciones. CONCLUSIÓN: Los hallazgos de este estudio pueden usarse como medida para mejorar el proceso encaminado a tratar a los pacientes con DACD.

Detection of Chlamydia trachomatis in an Australian high school student population.

OBJECTIVE: To assess the prevalence of Chlamydia trachomatis infections among an Australian high school adolescent population. METHODS: Over a 4 year period, 14 high schools were selected in which an infertility prevention programme targeting C. trachomatis was delivered to senior student populations. Coded first catch urine specimens were analysed by Amplicor PCR and infected students treated. Data retrospectively obtained from chlamydia screening programmes conducted among disadvantaged young people detached from formal education were also collated for comparison. RESULTS: Of a total student test population of 1174, 15 (1.3%; 95% CI 0.7% to 2.1%) were diagnosed with C. trachomatis. Of 516 females and 658 males, 12 (2.3%; 95% CI 1.1% to 4.1%) and 3 (0.5%; 95% CI 0.1% to 1.4%) were tested positive respectively. Data collated for three populations of disadvantaged youth returned at total of 89 C. trachomatis infections out of 560 people (15.9% 95%CI 13.0-19.2%). CONCLUSION: The overall prevalence of C. trachomatis infection among this population of senior high school adolescents is low, and significantly differs from the higher chlamydia rates detected in disadvantaged adolescents detached from formal schooling (p<0.0001).

TEP1, the yeast homolog of the human tumor suppressor gene PTEN/MMAC1/TEP1, is linked to the phosphatidylinositol pathway and plays a role in the developmental process of sporulation.

PTEN/MMAC1/TEP1 (PTEN, phosphatase deleted on chromosome ten; MMAC1, mutated in multiple advanced cancers; TEP1, tensin-like phosphatase) is a major human tumor suppressor gene whose suppressive activity operates on the phosphatidylinositol pathway. A single homologue of this gene, TEP1 (YNL128w), exists in the budding yeast Saccharomyces cerevisiae. Yeast strains deleted for TEP1 exhibit essentially no phenotype in haploids; however, diploids exhibit resistance to the phosphatidylinositol-3-phosphate kinase inhibitor wortmannin and to lithium ions. Although rates of cancer increase with age, neither tep1 haploids nor diploids have altered life spans. TEP1 RNA is present throughout the cell cycle, and levels are dramatically up-regulated during meiotic development. Although homozygous tep1 mutants initiate the meiotic program and form spores with wild-type kinetics, analysis of the spores produced in tep1 mutants indicates a specific defect in the trafficking or deposition of dityrosine, a major component of yeast spore walls, to the surface. Introduction of a common PTEN mutation found in human tumors into the analogous position in Tep1p produces a nonfunctional protein based on in vivo activity. These studies implicate Tep1p in a specific developmental trafficking or deposition event and suggest that Tep1p, like its mammalian counterpart, impinges on the phosphatidylinositol pathway.

Safety and Efficacy of Once-Daily Captopril Plus Hydrochlorothiazide versus Nifedipine Gastrointestinal Therapeutic System in Black Patients with Mild to Moderate Hypertension.

The safety and efficacy of captopril plus hydrochlorothiazide (HCTZ) were compared to nifedipine gastrointestinal therapeutic system (GITS) in 145 randomly assigned black patients with mild to moderate hypertension. Following a 4-week placebo lead-in, patients received captopril plus HCTZ 25/15 mg or nifedipine GITS 30 mg for up to 12 weeks. Upward dose titration was permitted at weeks 3 and 6. Mean seated systolic and diastolic blood pressures decreased 16.1 ± 13.5 mm Hg and 11.5 ± 7.4 mm Hg, respectively, with captopril plus HCTZ. Statistically similar decreases were observed with nifedipine GITS: systolic, 19.3 ± 12.2 mm Hg; diastolic, 13.8 ± 7.2 mm Hg. There were no clinically significant between-group differences in serum chemistries. Edema was reported in 20.3% of nifedipine GITS patients versus 1.4% of captopril plus HCTZ patients (p = 0.001). The two regimens were equally effective in controlling blood pressure in black patients; however, a higher incidence of edema occurred with nifedipine GITS compared to captopril plus HCTZ.

Effect of combination therapy with atenolol and the angiotensin-converting enzyme inhibitor benazepril.

The purpose of this study was to determine whether patients whose blood pressure failed to normalize while receiving monotherapy with atenolol would experience further blood pressure lowering by adding the angiotensin-converting enzyme (ACE) inhibitor benazepril hydrochloride to their treatment regimen. Seventy-four of the original 127 patients treated with atenolol met the criteria for entry into the 4-week, double-blind phase of the study, in which either benazepril 10 mg twice daily (increased after 1 week, if necessary, to 20 mg twice daily) or placebo was added to atenolol. At end point, 46% of the benazepril group had achieved an excellent or good response (ie, diastolic blood pressure [DBP] < 90 mm Hg or a decrease of > or = 10 mm Hg below the baseline) compared with 14% of the placebo group (P < 0.01). The mean fall in DBP at end point was -5.6 mm Hg in the benazepril group and -3.7 mm Hg in the placebo group. Because six patients in the benazepril group experienced an increase of blood pressure that offset the fall observed in the responders, the difference in DBP response between the benazepril group and the placebo group was not statistically significant. We conclude that adding benazepril to the regimen of patients whose blood pressure is inadequately controlled while receiving atenolol monotherapy can produce an additional decrease in blood pressure in almost half the patients.

Chronic therapy for congestive heart failure with benazepril HCl, a new angiotensin converting enzyme inhibitor.

Benazepril HCl is an orally effective angiotensin converting enzyme (ACE) inhibitor previously shown to have significant acute hemodynamic benefits in patients with congestive heart failure. In this study, 21 patients with New York Heart Association Class III or IV congestive heart failure were treated with 2 to 15 mg of benazepril HCl as a single daily oral dose for 28 days to determine the clinical and hemodynamic value of chronic therapy. Each patient underwent clinical evaluation during the 28-day period, as well as invasive hemodynamic studies on the first two and last two days of the trial. Plasma ACE activity and aldosterone levels fell significantly and renin levels rose after therapy. Benazepril HCl produced significant (p less than 0.01) reductions in arterial pressure and systemic vascular resistance, with corresponding increases in cardiac output and decreases in pulmonary artery wedge pressure. Responses after 28 days of therapy were equivalent to those after the initial doses. Clinical effects included reduced rest, exertional and paroxysmal nocturnal dyspnea, as well as reduced peripheral edema. Only one patient developed symptomatic orthostatic hypotension. Thus, benazepril HCl, given once daily, is an effective and well tolerated oral agent for the chronic treatment of advanced congestive heart failure.

Long-term therapy with benazepril in patients with congestive heart failure: effects on clinical status and exercise tolerance.

Benazepril hydrochloride (CGS 14824A) is an orally active, nonsulfhydryl compound that is transformed in vivo to a long-acting inhibitor of angiotensin-converting enzyme (ACE). Previous studies have shown benazepril to lower blood pressure in hypertensive patients and to confer acute hemodynamic benefits in patients with congestive heart failure (CHF). In the current multicenter investigation, 16 patients with chronic CHF due to left ventricular systolic dysfunction (ejection fraction less than 0.40 at rest) whose symptoms corresponded to New York Heart Association classes II to IV were given open-label benazepril once daily in ascending doses of 2 to 20 mg and followed biweekly for 12 weeks. Evaluation of the 15 subjects who completed the trial showed a progressive increase in treadmill exercise duration (from 7.65 +/- 3.64 [SD] minutes at baseline to 9.74 +/- 3.66 minutes at 12 weeks, P less than .001); augmentation of the mean left ventricular ejection fraction (from 0.266 +/- 0.133 at baseline to 0.292 +/- 0.136 at 12 weeks, P less than .025); relief of exertional dyspnea in 7 of the 15 patients (P less than .02); and improvement in global symptomatic status in 10 of the patients (P less than .01). These responses were accompanied by a reduction in serum ACE activity of 75% (from 27.2 +/- 10.5 IU/L at baseline to 6.7 +/- 1.9 IU/L at 12 weeks, P less than .001), which was independent of dose and duration of treatment. The magnitude of ACE inhibition did not correlate with changes in the efficacy variables. Aside from two instances of symptomatic hypotension (one of which was complicated by volume depletion), the drug was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Diurnal blood pressure in patients with mild-to-moderate hypertension treated with once-daily benazepril hydrochloride.

This study evaluated the blood pressure effects of administration of once daily oral benazepril hydrochloride, a new angiotensin-converting enzyme (ACE) inhibitor, for mild-to-moderate hypertension. After a 2 to 4 week placebo baseline period, patients with diastolic blood pressure between 95 and 114 mm Hg, were randomized to receive either placebo or benazepril hydrochloride, 5, 10, 20, or 40 mg, once daily in double-blind fashion for 28 days. Blood pressure was measured predose and at 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours after the dose during inpatient observation days at the end of the placebo baseline period, and on the first and last day of the double-blind treatment period; and 24 hours after the dose at weekly outpatient visits. All doses of benazepril hydrochloride resulted in clinically important reductions in diastolic and systolic blood pressures that lasted between 12 and 24 hours after both the first dose, and following the last dose after 4 weeks of treatment. The findings indicate that benazepril hydrochloride may be clinically useful as once-daily monotherapy in many patients with hypertension.

Pharmacodynamic dependent disposition of the angiotensin converting enzyme inhibitor, libenzapril.

Libenzapril, an angiotensin converting enzyme inhibitor, was administered to healthy male volunteers in a randomized, two-phase pharmacokinetic study. One phase compared the pharmacokinetics of a 4 mg intravenous infusion and 20 mg oral solution, and the other phase provided two additional intravenous infusions of 1.7 and 12 mg for comparison. The intravenous model-independent pharmacokinetic parameters MRTiv, Vss, CL, and CLr all exhibited dose dependence. The concentration dependent renal clearance was maximal at 83 mL/min and minimal at 32 mL/min following intravenous administration. The mechanism of libenzapril's self-inducible clearance appears to have a pharmacodynamic basis. The absolute bioavailability was estimated at less than 10% and the renal clearance following oral administration exhibited additional route dependency.

Intra- and intersubject variability: mixed-effects statistical analysis of repeated doses of an angiotensin converting enzyme inhibitor, CGS 16617.

The intrasubject and intersubject variabilities for CGS 16617, an angiotensin converting enzyme inhibitor, were evaluated in an open-label, repeat single-dose bioavailability trial. Eight healthy male volunteers each received a 20-mg oral dose of CGS 16617 as an aqueous solution on four separate occasions. Components of variance were evaluated for a mixed-effects statistical model in which subjects were regarded as a random factor. While intersubject variability was statistically significant (P less than 0.05) for all pharmacokinetic variables measured, AUC, Cmax, t1/2, and tmax, its contribution to the total observed variability was relatively small for AUC, t1/2, and tmax. The proportion of variation due to intrasubject variability was 70, 19, 61, and 72% for AUC, Cmax, t1/2, and tmax, respectively. Ramifications of the large intrasubject source component of variability as related to bioavailability trials and biological variation are discussed.

Acute management of major trauma involving the foot and ankle with Hoffmann external fixation.

Massive trauma involving the foot was treated by external fixation in 33 cases and followed for 1 to 3 years. Amputations were performed in seven (21%) because of uncontrollable deep sepsis in two and massive injury in five. The other 26 (79%) had functionally acceptable feet at follow-up, but all had some stiffness and cosmetic deformity. Complications attributed to the Hoffman external fixation were limited to three pin tract infections. We recommend Hoffmann external fixation when it is necessary to: 1) stabilize major open fracture dislocations; 2) maintain length where bone is lost or extensively comminuted; 3) prevent soft tissue contractures; 4) control joint position for delayed ankle arthrodesis; and 5) provide easy access for soft and bone tissue reconstructions.