Conversion of Vertical Banded Gastroplasty to Roux-en-Y Gastric Bypass Results in Restoration of the Positive Effect on Weight Loss and Co-morbidities: Evaluation of 101 Patients

BACKGROUND: Vertical banded gastroplasty (VBG) is a widely used restrictive procedure in bariatric surgery. However, the re-operation rate after this operation is high. In the case of VBG failure, a conversion to Roux-en-Y gastric bypass (RYGBP) is an option. A study was undertaken to evaluate the results of the conversion from VBG to RYGBP. METHODS: 101 patients had conversion from VBG to RYGBP. Patients were separated into 3 groups, based on the indication for conversion: weight regain (group 1), excessive weight loss (group 2) and severe eating difficulties (group 3). Data for the study were collected by retrospective analysis of prospectively recorded data. RESULTS: Weight regain (group 1) was the reason for conversion in 73.3% of patients. Staple-line disruption was the most important cause for the weight regain (74.3%). Excessive weight loss (group 2) affected 14% of patients and was caused by outlet stenosis in 78.6% of patients. The remaining 13% had severe eating difficulties as a result of outlet stenosis (46.1%), pouch dilatation (30.8%) and pouch diverticula (23.1%). Mean BMI before conversion to RYGBP was 40.5, 22.3 and 29.8 kg/m2 in group 1, 2 and 3, respectively. Minor or major direct postoperative complications were observed in 2.0% to 7.0%. Long-term complications were more frequent, and consisted mainly of anastomotic stenosis (22.7%) and incisional hernia (16.8%). Follow-up after conversion was achieved in all patients (100%), with a mean period of 38 +/- 29 months. BMI decreased from 40.5 to 30.1 kg/m2, increased from 22.3 to 25.3 kg/m2. and decreased slightly from 29.8 to 29.0 kg/m2 in group 1, 2 and 3, respectively. All patients in group 3 noticed an improvement in eating difficulties. CONCLUSION: Complications after conversion from failed VBG to RYGBP are substantial and need to be considered. However, the conversion itself is a successful operation in terms of effect on body weight and treating eating difficulties after VBG

Long Term Protection after Immunization with P. berghei Sporozoites Correlates with Sustained IFNγ Responses of Hepatic CD8+ Memory T Cells

Protection against P. berghei malaria can successfully be induced in mice by immunization with both radiation attenuated sporozoites (RAS) arresting early during liver stage development, or sporozoites combined with chloroquine chemoprophylaxis (CPS), resulting in complete intra-hepatic parasite development before killing of blood-stages by chloroquine takes place. We assessed the longevity of protective cellular immune responses by RAS and CPS P. berghei immunization of C57BL/6j mice. Strong effector and memory (TEM) CD8+ T cell responses were induced predominantly in the liver of both RAS and CPS immunized mice while CD4+ T cells with memory phenotype remained at base line levels. Compared to unprotected naïve mice, we found high sporozoite-specific IFNγ ex vivo responses that associated with induced levels of in vivo CD8+ TEM cells in the liver but not spleen. Long term evaluation over a period of 9 months showed a decline of malaria-specific IFNγ responses in RAS and CPS mice that significantly correlated with loss of protection (r2 = 0.60, p<0.0001). The reducing IFNγ response by hepatic memory CD8+ T cells could be boosted by re-exposure to wild-type sporozoites. Our data show that sustainable protection against malaria associates with distinct intra-hepatic immune responses characterized by strong IFNγ producing CD8+ memory T cells

Comparative assessment of An. gambiae and An. stephensi mosquitoes to determine transmission-reducing activity of antibodies against P. falciparum sexual stage antigens.

BACKGROUND: With the increasing interest in vaccines to interrupt malaria transmission, there is a demand for harmonization of current methods to assess Plasmodium transmission in laboratory settings. Potential vaccine candidates are currently tested in the standard membrane feeding assay (SMFA) that commonly relies on Anopheles stephensi mosquitoes. Other mosquito species including Anopheles gambiae are the dominant malaria vectors for Plasmodium falciparum in sub-Saharan Africa. METHODS: Using human serum and monoclonal pre-fertilization (anti-Pfs48/45) and post-fertilization (anti-Pfs25) antibodies known to effectively inhibit sporogony, we directly compared SMFA based estimates of transmission-reducing activity (TRA) for An. stephensi and An. gambiae mosquitoes. RESULTS: In the absence of transmission-reducing antibodies, average numbers of oocysts were similar between An. gambiae and An. stephensi. Antibody-mediated TRA was strongly correlated between both mosquito species, and absolute TRA estimates for pre-fertilisation monoclonal antibodies (mAb) showed no significant difference between the two species. TRA estimates for IgG of naturally exposed individuals and partially effective concentrations of anti-Pfs25 mAb were higher for An. stephensi than for An. gambiae. CONCLUSION: Our findings support the use of An. stephensi in the SMFA for target prioritization. As a vaccine moves through product development, better estimates of TRA and transmission-blocking activity (TBA) may need to be obtained in epidemiologically relevant parasite-species combination

Plasma Corticosterone Activates SGK1 and Induces Morphological Changes in Oligodendrocytes in Corpus Callosum

Repeated stressful events are known to be associated with onset of depression. Further, stress activates the hypothalamic–pituitary–adrenocortical (HPA) system by elevating plasma cortisol levels. However, little is known about the related downstream molecular pathway. In this study, by using repeated water-immersion and restraint stress (WIRS) as a stressor for mice, we attempted to elucidate the molecular pathway induced by elevated plasma corticosterone levels. We observed the following effects both, in vivo and in vitro: (1) repeated exposure to WIRS activates the 3-phosphoinositide-dependent protein kinase (PDK1)–serum glucocorticoid regulated kinase (SGK1)–N-myc downstream-regulated gene 1 (NDRG1)–adhesion molecule (i.e., N-cadherin, α-catenin, and β-catenin) stabilization pathway via an increase in plasma corticosterone levels; (2) the activation of this signaling pathway induces morphological changes in oligodendrocytes; and (3) after recovery from chronic stress, the abnormal arborization of oligodendrocytes and depression-like symptoms return to the control levels. Our data strongly suggest that these abnornalities of oligodendrocytes are possibly related to depression-like symptoms

Contemporary management of cancer of the oral cavity

Oral cancer represents a common entity comprising a third of all head and neck malignant tumors. The options for curative treatment of oral cavity cancer have not changed significantly in the last three decades; however, the work up, the approach to surveillance, and the options for reconstruction have evolved significantly. Because of the profound functional and cosmetic importance of the oral cavity, management of oral cavity cancers requires a thorough understanding of disease progression, approaches to management and options for reconstruction. The purpose of this review is to discuss the most current management options for oral cavity cancers

Protection against a malaria challenge by sporozoite inoculation.

Contains fulltext : 81826.pdf (publisher's version ) (Open Access)BACKGROUND: An effective vaccine for malaria is urgently needed. Naturally acquired immunity to malaria develops slowly, and induction of protection in humans can be achieved artificially by the inoculation of radiation-attenuated sporozoites by means of more than 1000 infective mosquito bites. METHODS: We exposed 15 healthy volunteers--with 10 assigned to a vaccine group and 5 assigned to a control group--to bites of mosquitoes once a month for 3 months while they were receiving a prophylactic regimen of chloroquine. The vaccine group was exposed to mosquitoes that were infected with Plasmodium falciparum, and the control group was exposed to mosquitoes that were not infected with the malaria parasite. One month after the discontinuation of chloroquine, protection was assessed by homologous challenge with five mosquitoes infected with P. falciparum. We assessed humoral and cellular responses before vaccination and before the challenge to investigate correlates of protection. RESULTS: All 10 subjects in the vaccine group were protected against a malaria challenge with the infected mosquitoes. In contrast, patent parasitemia (i.e., parasites found in the blood on microscopical examination) developed in all five control subjects. Adverse events were mainly reported by vaccinees after the first immunization and by control subjects after the challenge; no serious adverse events occurred. In this model, we identified the induction of parasite-specific pluripotent effector memory T cells producing interferon-gamma, tumor necrosis factor alpha, and interleukin-2 as a promising immunologic marker of protection. CONCLUSIONS: Protection against a homologous malaria challenge can be induced by the inoculation of intact sporozoites. (ClinicalTrials.gov number, NCT00442377.