Despite South Africa being one of the high-burden multidrug-resistant tuberculosis (MDR-TB) countries, information regarding the population structure of drug-resistant Mycobacterium tuberculosis strains is limited from many regions of South Africa. This study investigated the population structure and transmission patterns of drug-resistant M. tuberculosis isolates in a high-burden setting of South Africa as well as the possible association of genotypes with drug resistance and demographic characteristics. A total of 336 consecutive MDR-TB isolates from four provinces of South Africa were genotyped using spoligotyping and mycobacterial interspersed repetitive-unit–variable number tandem repeat (MIRU-VNTR) typing. Drug susceptibility testing for ofloxacin, kanamycin, and capreomycin was performed using the agar proportion method. The results showed that 4.8% of MDR-TB isolates were resistant to ofloxacin, 2.7% were resistant to kanamycin, and 4.5% were resistant to capreomycin, while 7.1% were extensively drug resistant (XDR), and the remaining 83.6% were susceptible to all of the second-line drugs tested. Spoligotyping grouped 90.8% of the isolates into 25 clusters, while 9.2% isolates were unclustered. Ninety-one percent of the 336 isolates were assigned to 21 previously described shared types, with the Beijing family being the predominant genotype in the North-West and Limpopo Provinces, while the EAI1_SOM family was the predominant genotype in the Gauteng and Mpumalanga Provinces. No association was found between genotypes and specific drug resistance patterns or demographic information. The high level of diversity and the geographical distribution of the drug-resistant M. tuberculosis isolates in this study suggest that the transmission of TB in the study settings is not caused by the clonal spread of a specific M. tuberculosis strain.
Control of rabies requires a consistent supply of dependable resources, constructive cooperation between veterinary and public health authorities, and systematic surveillance. These are challenging in any circumstances, but particularly during conflict. Here we describe available human rabies surveillance data from Iraq, results of renewed sampling for rabies in animals, and the first genetic characterisation of circulating rabies strains from Iraq. Human rabies is notifiable, with reported cases increasing since 2003, and a marked increase in Baghdad between 2009 and 2010. These changes coincide with increasing numbers of reported dog bites. There is no laboratory confirmation of disease or virus characterisation and no systematic surveillance for rabies in animals. To address these issues, brain samples were collected from domestic animals in the greater Baghdad region and tested for rabies. Three of 40 brain samples were positive using the fluorescent antibody test and hemi-nested RT-PCR for rabies virus (RABV). Bayesian phylogenetic analysis using partial nucleoprotein gene sequences derived from the samples demonstrated the viruses belong to a single virus variant and share a common ancestor with viruses from neighbouring countries, 22 (95% HPD 14–32) years ago. These include countries lying to the west, north and east of Iraq, some of which also have other virus variants circulating concurrently. These results suggest possible multiple introductions of rabies into the Middle East, and regular trans-boundary movement of disease. Although 4000 years have passed since the original description of disease consistent with rabies, animals and humans are still dying of this preventable and neglected zoonosis.
Control of rabies requires cooperation between government departments, consistent funding, and an understanding of the epidemiology of the disease obtained through surveillance. Here we describe human rabies surveillance data from Iraq and the results of renewed sampling for rabies in animals. In Iraq, it is obligatory by law to report cases of human rabies. These reports were collated and analysed. Reported cases have increased since 2003, with a marked increase in Baghdad 2009–2010. There is no system for detecting rabies in animals and the strains circulating in Iraq have not previously been characterized. To address this, samples were collected from domestic animals in Baghdad and tested for rabies. Three out of 40 were positive for rabies virus. Comparison of part of the viral genetic sequence with other viruses from the region demonstrated that the viruses from Iraq are more closely related to each other than those from surrounding countries, but diverged from viruses isolated in neighbouring countries approximately 22 (95% HPD 14–32) years ago. Although 4000 years have passed since the original description of disease consistent with rabies, animals and humans are still dying of this preventable and neglected zoonosis.
Shortages of health care workers (HCWs) represents a serious challenge to ensuring effective HIV care in resource-limited settings (RLS). Stress, motivation, and job satisfaction have been linked with HCW retention and are important in addressing HCW shortages. In this cross-sectional study HCW stress, motivation, and perceived ability to meet patient needs were assessed in PEPFAR-supported urban HIV care and treatment clinics (CTCs) in Tanzania.
A self-administered questionnaire measuring motivation, stress, and perceived ability to meet patient needs was given to HCWs at 16 CTCs. Scales measuring HCW satisfaction, motivation, and stress were developed using principle components analysis. Hierarchical linear models were used to explore the association of HCW and site characteristics with reported satisfaction, stress, motivation, and ability to meet patient needs.
Seventy-three percent (279) of HCWs completed the questionnaire. Most (73%) HCWs reported minimal/no work-related stress, with 48% reporting good/excellent motivation, but 41% also reporting feeling emotionally drained. Almost all (98%) reported feeling able to help their patients, with 68% reporting work as rewarding. Most reported receipt of training and supervision, with good availability of resources. In the multivariate model, direct clinical providers reported lower motivation than management (p<0.05) and HCWs at medium-sized sites reported higher motivation than HCWs at larger sites (p<0.05). HCWs at small and medium sites were more likely to feel able to help patients than those from larger sites (p<0.05 and p<0.001 respectively).
Despite significant patient loads, HCWs in these PEPFAR-supported CTCs reported high levels of motivation, job satisfaction, ability to meet patient needs, low levels of stress but significant emotional toll. Understanding the relationship between support systems such as strong supervision and training and these outcomes is critical in designing interventions to improve motivation, reduce stress and increase retention of HCWs.
HIV; motivation; stress; health care workers; resource limited settings
We describe here our experience in using sinus microdebrider to rapidly debulk and sculpt the tissues in cases of rhinophyma correction. We utilized the use of the 4 mm M4 Rotatable Cutting Straight Sinus Blade on a straight Straightshot M4 Microdebrider by Medtronic at 800 rpm oscillation which is normally utilised in our sinus surgery practice. The microdebrider is straightforward to use and is already stocked in most ENT departments. It requires no additional training or cost outlay for departments that perform endoscopic sinus surgery with microdebrider. In our experience it affords the surgeon the ability to rapidly and accurately sculpt the nose to an excellent aesthetic result. We feel it is a more precise tool than cold steel or Bovie cautery, quicker than CO2 laser techniques, and avoids the aerosol of dermabrasion. No complications occurred in our series, and all patients rated their cosmetic outcome as good to excellent.
Campylobacter concisus, a Gram-negative bacterium that colonizes the human oral cavity, has been shown to be associated with inflammatory bowel diseases (IBD). The effects of different C. concisus strains on intestinal epithelial expression of Toll like receptors (TLR) have not been investigated. This study examined the effects of C. concisus strains isolated from patients with IBD and controls on expression of TLR4, its co-receptor myeloid differentiation factor (MD)-2; TLR2, TLR5, cyclooxygenase-2 (COX-2) and interleukin (IL)-8 in HT-29 cells.
Fourteen oral and enteric C. concisus strains isolated from patients with IBD and healthy controls were co-incubated with HT-29 cells. Expression of TLR4, MD-2, TLR2, TLR5 and COX-2 in HT-29 cells in response to C. concisus infection was examined by Western blot, flow cytometry analysis and immunofluorescent staining visualized by confocal microscope. Production of IL-8 was evaluated by enzyme-linked immunosorbent assay.
Both oral and enteric C. concisus strains upregulated expression of TLR4 in HT-29 cells. The levels of glycosylated TLR4 (Gly-TLR4) and surface TLR4 induced by C. concisus strains isolated from patients with IBD were significantly higher than those induced by C. concisus strains isolated from the healthy controls. Four C. concisus strains isolated from patients with IBD induced more than two-fold increase of surface expression of MD-2. C. concisus did not affect expression of TLR2 and TLR5. All C. concisus strains induced production of IL-8 and COX-2 in HT-29 cells.
This study shows that some C. concisus strains, most from patients with IBD, upregulate surface expression of TLR4 and MD-2 in HT-29 cells. These data suggest that a potential role of specific C. concisus strains in modulating the intestinal epithelial responses to bacterial LPS needs to be investigated.
In the title benzoylhydrazide derivative, C17H18N2O, the dihedral angle between the benzene rings is 88.45 (8)° and the azomethine double bond adopts an E conformation. In the crystal, molecules are linked by N—H⋯O and C—H⋯O hydrogen bonds, forming a chain along the b axis.
The fight against diseases spread by mosquitoes and other insects has enormous environmental, economic and social consequences. Chemical insecticides remain the first line of defence but the control of diseases, especially malaria and dengue fever, is being increasingly undermined by insecticide resistance. Mosquitoes have a large repertoire of P450s (over 100 genes). By pinpointing the key enzymes associated with insecticide resistance we can begin to develop new tools to aid the implementation of control interventions and reduce their environmental impact on Earth. Recent technological advances are helping us to build a functional profile of the P450 determinants of insecticide metabolic resistance in mosquitoes. Alongside, the cross-responses of mosquito P450s to insecticides and pollutants are also being investigated. Such research will provide the means to produce diagnostic tools for early detection of P450s linked to resistance. It will also enable the design of new insecticides with optimized efficacy in different environments.
mosquito; malaria; dengue; pyrethroids; oxidases; detoxification
Background. Odontodysplasia is an uncommon condition. It can be localised or generalised, isolated or part of a syndrome. Case Report. We first report the case of an 8.5-year-old boy who presented with abnormally shaped teeth and multiple intraoral abscesses. Findings of clinical and radiographic examinations were consistent with those of generalised odontodysplasia. A 2-step, conservative treatment plan was executed with a 10-year followup. Step 1 was root canal treatment of nonvital teeth. Step 2 was crowning without preparation of new vital, erupted, and malformed teeth. The second case is that of a 12-year-old girl who presented with lack of teeth in the upper-left quadrant. The impacted teeth were exposed surgically, and fixed restoration was performed for temporary aesthetic improvement. Conclusion. Instead of tooth extraction, an approach previously used in similar cases, conservative management is feasible and offers better prosthetic treatment options for the future.
The objective of this study was to qualitatively evaluate young Egyptians’ perceptions, attitudes, knowledge and behaviour towards injuries before implementation of an extensive questionnaire about injuries among Egyptian youth. In 2008, five focus groups of three to nine participants each were conducted in Cairo, Egypt in Arabic to evaluate young Egyptians’ attitudes towards injuries, injury prevention, and their understanding of ‘accidents’ and fatalism. Participants were 14–26 years of age and were from medium to high socioeconomic status. Focus group participants noted that the concept of hadthah (‘accident’) signified an event determined by destiny, whereas esabah (‘injury’) was the result of human actions. The results of these focus groups indicate that young, educated Egyptians are interested in injury prevention programmes despite low confidence in the preventability of injuries.
We are developing a methodology for the noninvasive imaging of glucose transport in vivo with PET and 18F-labeled 6-fluoro-6-deoxy-d-glucose (18F-6FDG), a tracer that is transported but not phosphorylated. To validate the method, we evaluated the biodistribution of 18F-6FDG to test whether it is consistent with the known properties of glucose transport, particularly with regard to insulin stimulation of glucose transport.
Under glucose clamp conditions, rats were imaged at the baseline and under conditions of hyperinsulinemia.
The images showed that the radioactivity concentration in skeletal muscle was higher in the presence of insulin than at the baseline. We also found evidence that the metabolism of 18F-6FDG was negligible in several tissues.
18F-6FDG is a valid tracer that can be used in in vivo transport studies. PET studies performed under glucose clamp conditions demonstrated that the uptake of nonphosphorylated glucose transport tracer 18F-6FDG is sensitive to insulin stimulation.
glucose transport; radiopharmaceutical; PET; glucose clamp
Aim. Genitourinary fistulas are bothersome clinical entities not only for the patient but also for the treating surgeon as well. A lot of surgical procedures have been proposed; however, most of the fistulas can be easily treated with plain surgical techniques, such as the simple surgical closure of the fistula tract. Material and Method. The study was carried out in the urogynecology department of Ankara Etlik Zübeyde Hanım Maternity Training and Research Hospital. The study included 12 cases with vesicovaginal fistulas and 15 cases with rectovaginal fistulas. Twenty-six patients underwent simple surgical closure technique. The age, the referral time to the hospital, the longest diameter of the fistula opening, the hospitalization time, the follow-up period and identifiable risk factors of the patients were evaluated. Results. Caeserean section was detected as primary risk factor for vesicovaginal fistulas and prolonged labor was detected as the most important risk factor for rectovaginal fistulas. In our study, we found that the simple closure technique cured 91% of vesicovaginal fistulas and 93% of rectovaginal fistulas. Conclusion. The simple closure technique has very high cure rates for both vesicovaginal and rectovaginal fistulas when the longest diameter of the fistula openings is ≤5 mm.
The magnitude of shigellosis in developing countries is largely unknown because an affordable detection method is not available. Current laboratory diagnosis of Shigella spp. is laborious and time consuming and has low sensitivity. Hence, in the present study, a molecular-based diagnostic assay which amplifies simultaneously four specific genes to identify invC for Shigella genus, rfc for S. flexneri, wbgZ for S. sonnei, and rfpB for S. dysenteriae, as well as one internal control (ompA) gene, was developed in a single reaction to detect and differentiate Shigella spp. Validation with 120 Shigella strains and 37 non-Shigella strains yielded 100% specificity. The sensitivity of the PCR was 100 pg of genomic DNA, 5.4 × 104 CFU/ml, or approximately 120 CFU per reaction mixture of bacteria. The sensitivity of the pentaplex PCR assay was further improved following preincubation of the stool samples in Gram-negative broth. A preliminary study with 30 diarrhoeal specimens resulted in no cross-reaction with other non-Shigella strains tested. We conclude that the developed pentaplex PCR assay is robust and can provide information about the four target genes that are essential for the identification of the Shigella genus and the three Shigella species responsible for the majority of shigellosis cases.
Hereditary multiple intestinal atresia (HMIA), a presumed autosomal recessive disorder, is an unusual and rare form of recurrent intestinal atresia which can be associated with severe combined immunodeficiency (SCID). The combination of HMIA and SCID is invariably lethal. The authors describe this fatal association in two siblings. The parents are consanguineous and have three other normal healthy children. Both index cases had abnormal antenatal ultrasounds and were symptomatic after birth. The final diagnosis of HMIA with SCID was confirmed in both siblings. They were never able to receive enteral feeds, remained totally dependent on parenteral nutrition, had repeated episodes of sepsis and died after a very difficult neonatal intensive care course. In this article we have reviewed the clinical course and outcome of both cases. The existing literature on multiple intestinal atresia, HMIA and HMIA with immunodeficiency is also reviewed.
Chemotherapy-induced amenorrhea is a serious concern for women undergoing cancer therapy. This prospective randomized trial evaluated the use of gonadotropin-releasing hormone (GnRH) analog triptorelin to preserve ovarian function in women treated with chemotherapy for early-stage breast cancer.
Patients and Methods
Premenopausal women age 44 years or younger were randomly assigned to receive either triptorelin or no triptorelin during (neo)adjuvant chemotherapy and were further stratified by age (< 35, 35 to 39, > 39 years), estrogen receptor status, and chemotherapy regimen. Objectives included the resumption of menses and serial monitoring of follicle-stimulating hormone (FSH) and inhibin A and B levels.
Targeted for 124 patients with a planned 5-year follow-up, the trial was stopped for futility after 49 patients were enrolled (median age, 39 years; range, 21 to 43 years); 47 patients were treated according to assigned groups with four cycles of adriamycin plus cyclophosphamide alone or followed by four cycles of paclitaxel or six cycles of fluorouracil, epirubicin, and cyclophosphamide. Menstruation resumed in 19 (90%) of 21 patients in the control group and in 23 (88%) of 26 in the triptorelin group (P= .36). Menses returned after a median of 5.8 months (range, 1 to 19 months) after completion of chemotherapy in the triptorelin versus 5.0 months (range, 0 to 28 months) in the control arm (P= .58). Two patients (age 26 and 35 years at random assignment) in the control group had spontaneous pregnancies with term deliveries. FSH and inhibin B levels correlated with menstrual status.
When stratified for age, estrogen receptor status, and treatment regimen, amenorrhea rates on triptorelin were comparable to those seen in the control group.
The first examples of catalytic enantioselective ring-opening/cross-metathesis (EROCM) reactions that involve enol ethers are reported. Specifically, we demonstrate that catalytic EROCM of several oxa- and azabicycles, cyclobutenes and a cyclopropene with an alkyl- or aryl-substituted enol ether proceed readily in the presence of a stereogenic-at-Mo monopyrrolide-monoaryloxide. In some instances, as little as 0.15 mol % of the catalytically active alkylidene is sufficient to promote complete conversion within 10 minutes. The desired products are formed in up to 90% yield and >99:1 enantiomeric ratio (er) with the disubstituted enol ether generated in >90% Z selectivity. The enol ether of the enantiomerically enriched products can be easily differentiated from the terminal alkene through a number of functionalization procedures that lead to the formation of useful intermediates for chemical synthesis (e.g., efficient acid hydrolysis to afford the enantiomerically enriched carboxaldehyde). In certain cases, enantioselectivity is strongly dependent on enol ether concentration: larger equivalents of the cross partner leads to the formation of products of high enantiomeric purity (versus near racemic products with one equivalent). The length of reaction time can be critical to product enantiomeric purity; high enantioselectivity in reactions that proceed to >98% conversion in as brief a reaction time as 30 seconds can be nearly entirely eroded within 30 minutes. Mechanistic rationale that accounts for the above characteristics of the catalytic process is provided.
Despite the advances in diagnosis and treatment of oral squamous cell carcinoma (OSCC), mortality and morbidity rates have not improved over the past decade. A major drawback in diagnosis and treatment of OSCC is the lack of knowledge relating to how genetic instability in oral cancer genomes affects oral carcinogenesis. Hence, the key aim of this study was to identify copy number alterations (CNAs) that may be cancer associated in OSCC using high-resolution array comparative genomic hybridization (aCGH). To our knowledge this is the first study to use ultra-high density aCGH microarrays to profile a large number of OSCC genomes (n = 46). The most frequently amplified CNAs were located on chromosome 11q11(52%), 2p22.3(52%), 1q21.3–q22(54%), 6p21.32(59%), 20p13(61%), 7q34(52% and 72%),8p11.23–p11.22(80%), 8q11.1–q24.4(54%), 9q13–q34.3(54%), 11q23.3–q25(57%); 14q21.3–q31.1(54%); 14q31.3–q32.33(57%), 20p13–p12.3(54%) and 20q11.21–q13.33(52%). The most frequently deleted chromosome region was located on 3q26.1 (54%). In order to verify the CNAs from aCGH using quantitative polymerase chain reaction (qPCR), the three top most amplified regions and their associated genes, namely ADAM5P (8p11.23–p11.22), MGAM (7q34) and SIRPB1 (20p13.1), were selected in this study. The ADAM5P locus was found to be amplified in 39 samples and deleted in one; MGAM (24 amplifications and 3 deletions); and SIRPB1 (12 amplifications, others undetermined). On the basis of putative cancer-related annotations, two genes, namely ADAM metallopeptidase domain 9 (ADAM9) and maltase-glucoamylase alpha-glucosidase (MGAM), that mapped to CNA regions were selected for further evaluation of their mRNA expression using reverse transcriptase qPCR. The over-expression of MGAM was confirmed with a 6.6 fold increase in expression at the mRNA level whereas the fold change in ADAM9 demonstrated a 1.6 fold increase. This study has identified significant regions in the OSCC genome that were amplified and resulted in consequent over-expression of the MGAM and ADAM9 genes that may be utilized as biological markers for OSCC.
An unknown number of patients have had male to female gender transformation. Various surgical techniques have been employed to construct the neovagina. The more traditional techniques include inverted penile grafts and vascular pedicle grafts, but also the small bowel and sigmoid colon have been used. In this case, the authors present a patient who previously had a gender transformation from male to female with use of bowel for the neovagina. The patient presented with severe abdominal pain, fever and leukocytosis. A CT scan revealed retroperitoneal free air, and an x-ray examination with contrast through the neovagina showed leakage from the neovaginal top. The patient was treated conservatively with antibiotics and discharged after 7 days.
A large body of research has documented the prevalence and severity of menopausal symptoms, especially vasomotor symptoms, in breast cancer survivors and their impact on quality of life. Urinary symptoms as part of the constellation of menopausal symptoms, however, have received relatively little attention. Thus, less is known about the prevalence and severity of urinary symptoms in breast cancer survivors.
We conducted a systematic review of studies published between 1990 and 2010 to describe the prevalence and severity of urinary symptoms in breast cancer survivors.
We identified 16 eligible studies involving more than 2,500 women. Studies varied with respect to purpose, design, and nature of samples included; the majority used the same definition and assessment approach for urinary symptoms. Prevalence rates for symptoms ranged from 12% of women reporting burning or pain on micturition to 58% reporting difficulty with bladder control. Although in many studies the largest percentage of women rated symptoms as mild, as many as 23% reported severe symptoms.
Mild to moderate urinary symptoms are common in breast cancer survivors and some women report severe symptoms. Symptoms appear to adversely affect women’s quality of life. There is a need for additional research assessing the natural history of urinary symptoms using consensus definitions and validated measures in diverse populations. Nevertheless, this review suggests that clinicians should screen for urinary symptoms in breast cancer survivors and offer treatment recommendations or make referrals as appropriate.
breast cancer; menopause; urogenital system; survivorship
This study was conducted to examine the safety and efficacy of pioglitazone, a thiazolidinedione insulin sensitizer, in adult outpatients with major depressive disorder.
In a 12-week, open-label, flexible-dose study, 23 patients with major depressive disorder received pioglitazone monotherapy or adjunctive therapy initiated at 15mg daily. Subjects were required to meet criteria for abdominal obesity (waist circumference >35 in. in women and >40 in. in men) or metabolic syndrome. The primary efficacy measure was the change from baseline to Week 12 on the Inventory of Depressive Symptomatology (IDS) total score. Partial responders (≥25% decrease in IDS total score) were eligible to participate in an optional extension phase for an additional three months.
Pioglitazone decreased depression symptom severity from a total IDS score of 40.3 ± 1.8 to 19.2 ± 1.8 at week 12 (p<.001). Among partial responders (≥ 25% decrease in IDS total score), an improvement in depressive symptoms was maintained during an additional 3-month extension phase (total duration = 24 weeks) according to IDS total scores (p<.001). Patients experienced a reduction in insulin resistance from baseline to Week 12 according to the log homeostasis model assessment (−0.8 ± 0.75; p<.001) and a significant reduction in inflammation as measured by log highly- sensitive C-reactive protein (−0.87 ± 0.72; p<.001). During the current episode, the majority of participants (74%, n=17), had already failed at least one antidepressant trial. The most common side effects were headache and dizziness; no patient discontinued due to side effects.
These data are limited by a small sample size and an open-label study design with no placebo control.
Although preliminary, pioglitazone appears to reduce depression severity and improve several markers of cardiometabolic risk, including insulin resistance and inflammation. Larger, placebo-controlled studies are indicated.
Compared to the numerous broad screens for oncogene mutations in adult cancers, very few have been performed in pediatric solid tumors. To identify novel mutations and potential therapeutic targets in pediatric cancers, we performed a high-throughput Sequenom-based analysis in large sets of several major pediatric solid cancers, including neuroblastoma (NB), Ewing sarcoma (ES), rhabdomyosarcoma (RMS), and desmoplastic small round cell tumor (DSRCT).
We designed a highly multiplexed Sequenom-based assay to interrogate 275 recurrent mutations across 29 genes. Genomic DNA was extracted from 192 NB, 75 ES, 89 RMS, and 24 DSRCT samples. All mutations were verified by Sanger sequencing.
Mutations were identified in 13% of NB samples, 4% of ES samples, 21.1% of RMS samples, and no DSRCT samples. ALK mutations were present in 10.4% of NB samples. The remainder of NB mutations involved the BRAF, RAS, and MAP2K1 genes and were absent in samples harboring ALK mutations. Mutations were more common in embryonal RMS (ERMS) samples (28.3%) than alveolar RMS (ARMS) (3.5%). In addition to previously identified RAS and FGFR4 mutations, we report for the first time PIK3CA and CTNNB1 (Beta-Catenin) mutations in 4.9% and 3.3% of ERMS, respectively.
In ERMS, ES, and NB, we identified novel occurrences of several oncogene mutations recognized as drivers in other cancers. Overall, NB and ERMS contain significant subsets of cases with non-overlapping mutated genes in growth signaling pathways. Tumor profiling can identify a subset of pediatric solid tumor patients as candidates for kinase inhibitors or RAS-targeted therapies.
mutation; rhabdomyosarcoma; neuroblastoma; Ewing sarcoma; desmoplastic small round cell tumor
Young children, older children, and adults develop comparable levels and durations of immunity following cholera. In comparison, young children receiving oral killed cholera vaccines (OCV) develop a lower level and shorter duration of protection than those of older children and adults. The reasons for this are unclear. We investigated OCV-induced memory T cell responses in younger and older children and compared responses to those in children with cholera. We found that patients with cholera developed significant levels of toxin-specific effector memory T cells (TEM) with follicular helper and gut-homing characteristics. Older children (6 to 14 years of age) receiving two doses of OCV containing recombinant cholera toxin B subunit (rCTB) had more modest TEM responses with follicular helper and gut-homing characteristics, but younger vaccinees (24 to 71 months of age) did not develop TEM responses. The TEM response correlated positively with subsequent IgG memory B cell responses specific to rCTB in older vaccinees. Cytokine analyses indicated that cholera patients developed significant Th1, Th17, and Th2 responses, while older children receiving vaccine developed more modest increases in Th1 and Th17 cells. Younger vaccinees had no increase in Th1 cells, a decrease in Th17 cells, and an increase in regulatory T (Treg) cells. Our findings suggest that T cell memory responses are markedly diminished in children receiving OCV, especially young children, compared to responses following naturally acquired cholera, and that these differences affect subsequent development of memory B cell responses. These findings may explain the lower efficacy and shorter duration of protection afforded by OCV in young children.
Aromatic compounds (biogenic and anthropogenic) are abundant in the biosphere. Some of them are well-known environmental pollutants. Although the aromatic nucleus is relatively recalcitrant, microorganisms have developed various catabolic routes that enable complete biodegradation of aromatic compounds. The adopted degradation pathways depend on the availability of oxygen. Under oxic conditions, microorganisms utilize oxygen as a cosubstrate to activate and cleave the aromatic ring. In contrast, under anoxic conditions, the aromatic compounds are transformed to coenzyme A (CoA) thioesters followed by energy-consuming reduction of the ring. Eventually, the dearomatized ring is opened via a hydrolytic mechanism. Recently, novel catabolic pathways for the aerobic degradation of aromatic compounds were elucidated that differ significantly from the established catabolic routes. The new pathways were investigated in detail for the aerobic bacterial degradation of benzoate and phenylacetate. In both cases, the pathway is initiated by transforming the substrate to a CoA thioester and all the intermediates are bound by CoA. The subsequent reactions involve epoxidation of the aromatic ring followed by hydrolytic ring cleavage. Here we discuss the novel pathways, with a particular focus on their unique features and occurrence as well as ecological significance.
We report the mutational analysis of an artificial oxygen transport protein, HP-7, which operates via a mechanism akin to human neuroglobin and cytoglobin. This protein destabilizes one of two heme-ligating histidine residues by coupling histidine side chain ligation with the burial of three charged glutamate residues on the same helix. Replacement of these glutamate residues with alanine, which is uncharged, increases the affinity of the distal histidine ligand by a factor of thirteen. Paradoxically, it also decreases heme binding affinity by a factor of five in the reduced state and sixty in the oxidized state. Application of a three-state binding model, in which an initial pentacoordinate binding event is followed by a protein conformational change to hexacoordinate, provides insight into the mechanism of this seemingly counterintuitive result: the initial pentacoordinate encounter complex is significantly destabilized by the loss of the glutamate side chains, and the increased affinity for the distal histidine only partially compensates. These results point to the importance of considering each oxidation and conformational state in the design of functional artificial proteins.
The aim of this study was to evaluate the effects of repeated porcelain firing process on the corrosion rates of the dental alloys.
MATERIALS AND METHODS
Cr-Co, Cr-Ni and Pd-Ag alloys were used for this study. Each metal supported porcelain consisted of 30 specimens of 10 for 7, 9 and 11 firing each. Disc-shaped specimens 10 mm diameter and 3 mm thickness were formed by melting alloys with a propane-oxygen flame and casted with a centrifuge casting machine and then with the porcelain veneer fired onto the metal alloys. Corrosion tests were performed in quintuplicate for each alloy (after repeated porcelain firing) in Fusayama artificial saliva solution (pH = 5) in a low thermal-expansion borosilicate glass cell. Tamhane and Sheffe test was used to compare corrosion differences in the results after repeated firings and among 7, 9 and 11 firing for each alloy. The probability level for statistical significance was set at α=0.05.
The corrosion resistance was higher (30 mV), in case of 7 times firing (Commercial). On the other hand, it was lower in case of 11 times firing (5 mV) (P<.05).
Repeated firings decreased corrosion resistance of Pd-Ag, Cr-Co and Cr-Ni alloys. The Pd-Ag alloy exhibited little corrosion in in vitro tests. The Cr-Ni alloy exhibited higher corrosion resistance than Cr-Co alloys in in vitro tests.
Alloys; Corrosion test; Repeated firings