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Little is known about the molecular mechanisms underlying the release of merozoites from malaria infected erythrocytes. In this study membranous structures present in the culture medium at the time of merozoite release have been characterized. Biochemical and ultrastructural evidence indicate that membranous structures consist of the infected erythrocyte membrane, the parasitophorous vacuolar membrane and a residual body containing electron dense material. These are subcellular compartments expected in a structure that arises as a consequence of merozoite release from the infected cell. Ultrastructural studies show that a novel structure extends from the former parasite compartment to the surface membrane. Since these membrane modifications are detected only after merozoites have been released from the infected erythrocyte, it is proposed that they might play a role in the release of merozoites from the host cell

The following questions and recommendations are pertinent to the following: TARGET POPULATION: These recommendations apply to adults with progressive GBM who have undergone standard primary treatment with surgery and/or chemoradiation. QUESTION 1: In adults with progressive glioblastoma is the use of bevacizumab as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?, Recommendation: Level III: Treatment with bevacizumab is suggested in the treatment of progressive GBM, as it provides improved disease control compared to historical controls as measured by best imaging response and progression free survival at 6 months, while not providing evidence for improvement in overall survival. QUESTION 2: In adults with progressive glioblastoma is the use of bevacizumab as combination therapy with cytotoxic agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?, Recommendation: Level III: There is insufficient evidence to show benefit or harm of bevacizumab in combination with cytotoxic therapies in progressive glioblastoma due to a lack of evidence supporting a clearly defined benefit without significant toxicity. QUESTION 3: In adults with progressive glioblastoma is the use of bevacizumab as a combination therapy with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?, Recommendation: There is insufficient evidence to support a recommendation regarding this question. QUESTION 4: In adults with progressive glioblastoma is the use of targeted agents as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?, Recommendation: There is insufficient evidence to support a recommendation regarding this question. QUESTION 5: In adults with progressive glioblastoma is the use of targeted agents in combination with cytotoxic therapies superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?, Recommendation: There is insufficient evidence to support a recommendation regarding this question. QUESTION 6: In adults with progressive glioblastoma is the use of immunotherapy monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?, Recommendation: There is insufficient evidence to support a recommendation regarding this question. QUESTION 7: In adults with progressive glioblastoma is the use of immunotherapy in combination with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?, Recommendation: There is insufficient evidence to support a recommendation regarding this question. QUESTION 8: In adults with progressive glioblastoma is the use of immunotherapy in combination with bevacizumab superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?, Recommendation: There is insufficient evidence to support a recommendation regarding this question., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To challenge the prevalent pessimism regarding the outcome of patients with metastases in the brainstem resulting in the use of whole brain radiation for palliation rather than stereotactic radiosurgery for definitive control and preservation of quality of life. We present our single institution review of the efficacy and safety of treating brainstem metastases aggressively with GKRS., Methods: Forty-one patients with 45 total lesions treated with GKRS were included. Mean age was 58.7 years, ranging from 22 to 82. Tumor volumes were objectively calculated, treatment effects assessed on imaging and clinical data collected and correlated to the radiosurgical response., Results: Mean survival after diagnosis of BSM was 11.6 months, ranging from 1.4 to 58.8 months. Margin dose ranged from 12 to 20 Gy. At first follow up, 11 (27%) patients had complete resolution of the treated lesion. At the second follow up 15 (37%) and third follow up 19 (46%) patients had a complete response. On average, there was a 64% decrease in tumor size at first follow up after treatment. 25 (61%) patients received WBRT in addition to radiosurgery; 16 (39%) received radiosurgery alone. There was no difference in overall survival between the two groups (p = 0.1324). ARE was seen in one patient who received  16 Gy to the margin of a 2.06 cm 3 pontine tumor, but without correlative symptoms. One patient was treated with Bevacizumab ® for progressive, but asymptomatic, edema following treatment that was not controlled by corticosteroids., Conclusions: Location in brainstem should not be a deterrent to the use of radiosurgery for these patients. The addition or exclusion of WBRT should be based on the clinical progression of the patient and within the limits of this study does not seem to impact overall survival. With improved survival as a result of better systemic therapy, these patients can benefit from better preservation of cognitive function by this strategy.

Background: Normal sagittal cervical alignment has been associated with improved outcome after anterior cervical discectomy and fusion (ACDF)., Objective: The aim of this study is to identify alterations of cervical sagittal balance parameters after single-level ACDF and assess correlations with postoperative functionality., Methods: A retrospective chart review was performed between January 2010 and January 2014 to identify adult patients with no previous cervical spine surgery who underwent ACDF at any one level between C2 and C7 for the single-level degenerative disease. Tumor, infection, and trauma cases were excluded from the study. For the included cases, the following data were recorded preoperatively and 6 months-1 year after surgery: sagittal balance-marker measurements of the C1-C2 angle, C2-C7 angle, C7 slope, segmental angle at the operated level, and sagittal vertical axis (SVA) distance between C2 and C7, as well as the neck disability index and visual analog scale of pain., Results: The present study included 47 patients (average age: 51.2 years; range: 28-86 years). A moderate negative correlation between a smaller C2-C7 angle and the presence of right arm pain before treatment was found ( P = 0.0281). Postoperatively, functionality scores significantly improved in all patients. C1-C2 angle increased with statistical significance ( P = 0.0255). C2-C7 angle, segmental angle, C7 slope, and SVA C2-C7 distance did not change with statistical significance after surgery. C7 slope significantly correlated with overall cervical sagittal balance ( P < 0.05)., Conclusions: Single-level ACDF significantly increases upper cervical lordosis (C1-C2) without significantly changing lower cervical lordosis (C2-C7). The C7 slope is a significant marker of overall cervical sagittal alignment ( P < 0.05)., Competing Interests: There are no conflicts of interest.

Purpose/objectives: The purpose of this study was to evaluate the effect of the number of brain lesions for which stereotactic radiosurgery (SRS) was performed on the dose volume relationships in normal brain., Materials and Methods: Brain tissue was segmented using the patient's pre-SRS MRI. For each plan, the following data points were recorded: total brain volume, number of lesions treated, volume of brain receiving 8 Gy (V8), V10, V12, and V15., Results: A total of 225 Gamma Knife® treatments were included in this retrospective analysis. The number of lesions treated ranged from 1 to 29. The isodose for prescription ranged from 40 to 95% (mean 55%). The mean prescription dose to tumor edge was 18 Gy. The mean coverage, selectivity, conformity, and gradient index were 97.5%, 0.63, 0.56, and 3.5, respectively. The mean V12 was 9.5 cm3 (ranging from 0.5 to 59.29). There was no correlation between the number of lesions and brain V8, V12, V10, or V15. There was a direct and statistically significant relationship between the brain volume treated (V8, V10, V12, and V15) and total volume of tumors treated (p < 0.001). In our study, the integral dose to the brain exceeded 3 J when the total tumor volume exceeded 25 cm3., Conclusions: The number of metastatic brain lesions treated bears no significant relationship to total brain tissue volume treated when using SRS. The fact that the integral dose to the brain exceeded 3 J when the total tumor volume exceeded 25 cm3 is useful for establishing guidelines. Although standard practice has favored using whole brain radiation therapy in patients with more than 4 lesions, a significant amount of normal brain tissue may be spared by treating these patients with SRS. SRS should be carefully considered in patients with multiple brain lesions, with the emphasis on total brain volume involved rather than the number of lesions to be treated., (© 2017 S. Karger AG, Basel.)

Purpose: Bevacizumab has been shown to increase progression free and overall survival in patients with metastatic colorectal cancer. Neoadjuvant bevacizumab is commonly used in patients undergoing liver resection. Our purpose was to evaluate whether bevacizumab is associated with increased rate of perioperative complications in patients undergoing hepatic resection for colorectal liver metastases (CRLM)., Methods: Retrospective analysis of patients undergoing hepatic resection for CRLM who received chemotherapy and bevacizumab (group 1, n = 134), or chemotherapy alone (group 2, n = 57). We compared demographics, surgical characteristics, and perioperative course., Results: Perioperative complications developed in 35 % of patients in group 1, and 47 % in group 2 (p = 0.11). Of those complications, 15 (11.2 %) in group 1, and 5 (8.8 %) in group 2 were considered major (p = 0.617). Four patients, all of whom received preoperative bevacizumab, developed enteric leaks following combined liver and bowel resection. The rate of anastomotic leak in group 1 was 10 %, compared with 0 in group 2, p = 0.56., Conclusion: Neoadjuvant chemotherapy along with bevacizumab was not associated with an increased risk of postoperative complications after hepatic resection. Possible association of increased morbidity with simultaneous bowel and liver resections following bevacizumab administration was found and we recommend avoiding such treatment combination.

Erythrocytes infected with the human malaria parasite Plasmodium falciparum become structurally and antigenically modified as a consequence of intracellular parasite development. The new antigens that appear on the surface of the infected erythrocyte originate from parasite-encoded proteins and by modification of the erythrocyte membrane protein band 3. Here, we show that anti-peptide antibodies generated against an amino acid sequence (YETFSKLIKIFQDH) of human band 3, and previously identified as mediating adhesion of infected erythrocytes to CD36, recognized P. falciparum-infected erythrocytes. In addition, sera from individuals living in a malaria endemic area (and who are presumably immune) contained immunoglobulins specific for this region of band 3. The anti-peptide antibodies reacted with the surface excrescences (knobs) on falciparum-infected erythrocytes. In uninfected erythrocytes, the band 3 region was cryptic and its exposure on the falciparum-infected erythrocyte surface required clustering of band 3 protein. Thus, a parasite-induced modification of band 3 promotes adhesion and induces antigenic changes in the P. falciparum-infected erythrocyte.

Sequestration in the microvessels of the deep tissues is a signal characteristic of the human malaria Plasmodium falciparum. The adhesion of P. falciparum-infected cells to the post-capillary endothelial cells in various tissues contributes to both the pathology of the disease (i.e. organ infarcts and coma) and parasite survival (i.e. the microaerophilic environment favors plasmodial growth while avoiding passage through and destruction in the spleen). This report identifies a conformational change in a region of band 3 protein involved in the enhanced adhesiveness of P. falciparum-infected erythrocytes.

The role of the erythrocyte anion exchanger, band 3 protein (AE1), in the adhesion of Plasmodium falciparum-infected erythrocytes to CD36 and thrombospondin (TSP) was studied. Two specific anion exchange inhibitors that bind covalently to different regions of the band 3 molecule affected cytoadherence in dissimilar ways. Modification of lysine 539 by diisothiocyanostilbene sulfonic acid (DIDS) resulted in a significant reduction in the adhesive properties of parasitized erythrocytes for CD36, but not TSP, whereas treatment with fluorescein-5-maleimide, which modifies lysine 430, was without effect on both TSP and CD36 binding. The adhesive properties of the DIDS binding region (DBR) was demonstrated by competition experiments using synthetic peptides and by direct interaction of such peptides with CD36 transfected CHO cells. The results suggest that host membrane proteins such as AE1 contribute to the adhesion of malaria-infected erythrocytes to CD36.

The human malaria parasite, Plasmodium falciparum, ages the red blood cell during its intracellular development. During this process of erythrocyte senescence the parasitized cell becomes less dense and deformable, its biconcave disc shape becomes more spherical and is covered with microscopic protuberances (knobs); the amounts of membrane cholesterol and phospholipids are altered and phosphatidylserine (PS) is externalized. The malaria-infected cell is osmotically fragile, more permeable to a wide variety of molecules via new permeation pathways (NPP), and there is surface deposition of immunoglobulins and complement. There are declines in sialic acid, reduced glutathione, tocopherol and ATP. Hemichromes are deposited on the inner surface of the red cell membrane and there is clustering of the anion transporter, band 3 protein, as well as exposure of neoantigens which contribute to antigenic variation and adhesivity of the parasitized erythrocyte. These time-dependent changes result from oxidative assault and a combination of factors, including a decline in levels of anti-oxidants and ATP coupled with an enhanced flux of ions especially calcium. Despite these parasite-induced age effects P. falciparum is able to avoid destruction by splenic removal through microvessel sequestration in the deep tissues via PS, clustered band 3 protein and adhesive neoantigens.

Infected erythrocytes containing the more mature stages of the human malaria Plasmodium falciparum may adhere to endothelial cells and uninfected red cells. These phenomena, called sequestration and rosetting, respectively, are involved in both host pathogenesis and parasite survival. This review provides a critical summary of recent advances in the characterization of the molecules of the infected red blood cell involved in adhesion, i.e. parasite-encoded molecules (PfEMP1, MESA, rifins, stevor, clag 9, histidine-rich protein), a modified host membrane protein (band 3) and exofacial exposure of phosphatidylserine, as well as receptors on the endothelium, i.e. thrombospondin, CD36, ICAM-1 (intercellular adhesion molecule), and chondroitin sulfate.

Monoclonal antibodies recognizing proteins localized to a unique subcellular compartment within the malaria parasite are described in this report. These monoclonal antibodies recognize Plasmodium falciparum proteins of 68, 45 and 22 kDa proteins which are also conserved in rodent Plasmodium species. Co-localization studies indicate that these proteins are located in a brefeldin A-induced compartment which was previously proposed to be an early step in the export of proteins from the parasite into the infected erythrocyte. COPII coat proteins, Sar1p and Sec31p, and the endoplasmic reticulum-associated chaperone, BiP, all partially co-localize with the 68 and 22 kDa proteins, thus suggesting that this subcellular compartment has some similarities to the endoplasmic reticulum or that this compartment represents a domain of the endoplasmic reticulum. The 68 and 22 kDa proteins are highly soluble in non-ionic detergent and are likely to be located within the lumen of a membrane-bound compartment. These proteins found within this subcellular compartment are present throughout the blood stage from very early rings to segmenters. The results of this study further substantiate the existence of an alternate secretory pathway in the malaria parasite which plays a role in the export of proteins into the host erythrocyte.

Little is known about the molecular mechanism underlying the release of merozoites from malaria-infected erythrocytes. In the present study, video microscopy was carried out, and images throughout the process of merozoite release from Plasmodium falciparum-infected erythrocytes were digitized and analyzed. Merozoites were shown to escape from the infected host cell in about 1 s through a single site of the infected erythrocyte membrane, whose dimension was estimated to be 2.5 microm. Merozoites were released together with the residual body containing hemozoin, leaving behind a membranous structure that persisted even after an extended period of observation. Densitometric measurements showed that the cytoplasmic content of the infected erythrocyte did not diffuse out as parasites were released, but was gradually lost thereafter. This would indicate that the release of merozoites from infected erythrocytes is not mediated by an explosive event.

An immunoprecipitation technique using biotin-labeled proteins of Taenia solium was developed to identify antigens recognized by immunoglobulins from patients with neurocysticercosis. Six major polypeptides of 100, 70, 50, 42, 35, and 24 kDa were recognized by cerebrospinal fluid from most serologically positive patients. All polypeptides except the 70- and 35-kDa antigens were retained on a lentil-lectin chromatography column and were recognized by lentil lectin in an overlay assay. The 70- and 35-kDa antigens were not labeled with biotin hydrazide, indicating that saccharide residues are not present in these two polypeptides. Furthermore, the 70- and 35-kDa antigens were recognized by antibodies of more than 86% of patients serologically positive for neurocysticercosis as opposed to none of the patients afflicted with other neuropathologies of the central nervous system. This finding indicates that immunodiagnosis of neurocysticercosis can be carried out with antigens different from those used in the standard enzyme-linked immunoelectrotransfer assay.

The mere exposure effect was examined in patients with mild to moderate Alzheimer's disease (AD). Twenty patients and 20 elderly controls judged the physical characteristics of faces. Implicit memory was tested later by presenting pairs of faces (old and new) and asking participants which faces they liked better. Patients and controls exhibited above chance preference for previously exposed faces. Experiment 2 evaluated whether the preserved implicit memory of patients was mediated by explicit memory. Patients and controls again judged faces but then later chose which faces they had seen before. Patients exhibited impaired recognition memory compared to controls. These findings suggest that a mere exposure effect for unfamiliar faces is present in mild to moderate AD. The results are discussed in terms of perceptual and conceptual priming and relatively spared occipital lobe functioning in early AD.

Three groups of informants--two in California, one in Atlanta--recalled their experiences of the 1989 Loma Prieta earthquake shortly after the event and again 11/2 years later. The Californians' recalls of their own earthquake experiences were virtually perfect. Even their recalls of hearing the news of an earthquake-related event were very good: much higher than Atlantan recalls of hearing about the quake itself. Atlantans who had relatives in the affected area remembered significantly more than those who did not. These data show that personal involvement in the quake led to greatly improved recall, but do not show why. Many Californian informants reported low levels of stress/arousal during the event; arousal ratings were not significantly correlated with recall. The authors suggest that repeated narrative rehearsals may have played an important role.

This research examined whether source memory is preserved in patients with mild to moderate Alzheimer's disease (AD). In Experiment 1, AD patients and normal elderly controls recalled true facts (information acquired outside of the experimental setting) and made-up facts (information acquired in the experiment), and they determined the source of these memories. Relative to controls, AD patients recalled fewer facts, but when they remembered this information, they attributed their learning to the correct source. In Experiment 2, memory of made-up facts was equated between groups by incorporating a 1-week recall delay for the controls. Again, AD patients accurately determined whether facts were learned inside or outside of the experiment. However, both groups performed at chance in terms of their memory for whether a made-up fact was read on a card or told by the examiner. The findings indicate relative preservation of source memory in the earliest stages of AD and are discussed in terms of methodological problems in testing source memory in impaired groups and in terms of frontal-lobe functioning.

Background: The preservation of implicit memory function during anesthesia is controversial, with conflicting results appearing in the literature. This study was designed to elucidate the effect of midazolam as part of an anesthetic technique on implicit memory function during anesthesia. Using a prospective randomized, double-blind study design, performance in three tasks (category generation, free association, and homophone spelling) was assessed., Methods: Forty-eight consenting patients were assigned to two equal groups, to receive 2 mg intravenous midazolam or normal saline before induction of anesthesia. Anesthesia was induced with fentanyl and propofol and maintained with isoflurane 1.3 MAC until incision and isoflurane 1.0 MAC in 70% nitrous oxide thereafter. Fentanyl was used for supplementation of anesthesia. During anesthesia, one of two 50-min tapes containing the test material was played to each patient on a portable cassette player. In the postanesthesia care unit and 48 h after surgery, patients were engaged in three tasks by an observer unaware of the treatment group or tape., Results: No significant main effect of priming or midazolam was observed in any of the tasks. In the word-association task, an interaction was observed between priming and treatment group (F = 9.62, P < .01) due to negative priming in the placebo group., Conclusions: The lack of a main effect of priming in any of the three tasks is consistent with the conclusion that indirect memory was not demonstrated for events occurring during the standard anesthetic conditions of this study. Further, midazolam appeared to have no effect.