Patients with COPD are associated with poor pulmonary anti-bacterial innate defenses, which increase the risk for frequent acute exacerbations caused by bacterial infection. Despite elevated numbers of phagocytes (macrophages and neutrophils), airways of patients with COPD show stable bacterial colonization. A defect in the phagocytic ability of alveolar macrophages (AMs) is one of the primary reasons for failure to clear the invading bacteria in airways of smokers and COPD patients and also in mice exposed to cigarette smoke (CS). Oxidative stress, as a result of CS exposure is implicated; however, the factors or mediators that inhibit phagocytic activity of AMs in lungs of smokers remain unclear. In the current study, we provide evidence that accumulation of oxidized phospholipids (Ox-PLs) mediate inhibition of phagocytic function of AMs in CS-exposed mice. Mice exposed to 6 months of CS showed impaired bacterial phagocytosis and clearance by AMs and elevated levels of Ox-PLs in bronchoalveolar lavage fluid (BALF), compared to mice exposed to room air. Intratracheal instillation of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OX-PAPC) inhibited phagocytic activity of AMs and impaired pulmonary bacterial clearance in mice. In vitro studies demonstrated that exposure of J774 macrophages to OX-PAPC inhibited bacterial phagocytosis and clearance. However, pre-treatment of OX-PAPC with the monoclonal antibody EO6, which specifically binds to oxidized phospholipid but not native phospholipid, abolished OX-PAPC induced inhibition of bacterial phagocytosis and clearance. Incubation of BALF retrieved from CS-exposed mice impaired bacterial phagocytosis by J774 macrophages, which was abolished by pre-treatment of BALF with the EO6 antibody. In conclusion, our study shows that Ox-PLs generated following chronic CS exposure could play a crucial role in inhibiting phagocytic function of AMs and thus impair pulmonary anti-bacterial innate defenses in CS-exposed mice. Therapeutic approaches that augment pulmonary antioxidant defenses could be beneficial in reducing oxidative stress-driven impairment of phagocytosis by AMs in smokers and COPD patients.
COPD; macrophages; oxidized phospholipids; bacteria; phagocytosis; cigarette smoke
The role of CD4+ T cells in the generation of therapeutic primary and memory immune responses in cancer diverse immunotherapy settings remains ambiguous. We herein investigated this issue using two vaccine formulations containing a novel costimulatory molecule, SA-4-1BBL, as adjuvant and HPV E7 or survivin (SVN) as tumor associated antigens (TAAs) in two mouse transplantable tumor models; the TC-1 cervical cancer expressing xenogeneic HPV E7 and 3LL lung carcinoma overexpressing autologous SVN. Single vaccination with optimized SA-4-1BBL/TAA formulations resulted in the eradication of 6-day established TC-1 and 3LL tumors in >70% of mice in both models. The in vivo depletion of CD4+ T cells one day before tumor challenge resulted in compromised vaccine efficacy in both TC-1 (25%) and 3LL (12.5%) tumor models. In marked contrast, depletion of CD4+ T cells 5 days post-tumor challenge and one day prior to vaccination did not significantly alter the therapeutic efficacy of these vaccines. However, long-term immunological memory was compromised in the 3LL, but not in TC-1 model as a significant number (85.7%) of tumor free-mice succumbed to tumor growth when rechallenged with 3LL cells 60 days after the initial tumor inoculation. Collectively, these results demonstrate the indispensable role CD4+ T cells play in the generation of therapeutic primary immune responses elicited by SA-4-1BBL/TAA-based vaccines irrespective of the nature of TAAs and establish the importance of CD4+ T cells for long-term immune memory against 3LL tumor expressing self-antigen SVN, but not TC-1 expressing xenogeneic viral antigen E7.
Geobacillus sp. strain WSUCF1 is a thermophilic spore-forming member of the phylum Firmicutes, isolated from a soil sample collected from the compost facility. We report the draft genome sequence of this isolate with an estimated genome size of 3.4 Mb. The genome sequence of this isolate revealed several genes encoding glycoside hydrolases, making it a potential candidate for plant biomass degradation.
Advances in medical therapies have greatly improved survivorship rates in children diagnosed with brain tumor; as a result, morbidities associated with survivorship have become increasingly important to identify and address. In general, pediatric posterior fossa tumor survivors tend to be less physically active than peers. This may be related to late effects of diagnosis and treatment, including cardiovascular, endocrine, psychological, and neurocognitive difficulties. Exercise has been shown to be effective in improving physical functioning, mood, and even cognitive functioning. Consequently, the benefits of physical exercise need to be explored and incorporated into the daily lives of pediatric posterior fossa tumor survivors. The primary aim of the present study was to establish the feasibility and safety of cardiorespiratory fitness testing in pediatric posterior fossa tumor survivors who had received cranial radiation therapy. Additionally, comparing our cohort to previously published data, we found that pediatric posterior fossa tumor survivors tended to be less fit than children with pulmonary disease as well as healthy controls, and approximately as fit as children with chronic heart disease and survivors of other types of childhood cancer. The importance of cardiorespiratory fitness in pediatric posterior fossa tumor survivors is discussed along with implications for future directions.
Pediatric posterior fossa tumor; Cardiorespiratory fitness; VO2max testing; Pediatric brain tumor
Context (Background): The tibial shaft is one of the most common sites of open fractures. The specific methods of skeletal stabilization and soft tissue treatment of open fractures continue to be topics of debate in the orthopaedic traumatology.
Aims: To evaluate the results of the intramedullary nailing in the open fractures of the tibia, especially in the Indian scenario.
Settings and Design: An observational, descriptive study which was done at a tertiary care hospital from 2006 to 2010.
Material and Methods: A prospective study was done on thirty cases which had sustained open fractures of t/hable Gustilo and Anderson grades I, II and III, who were operated for primary intramedullary interlocking nail fixation after thorough debridement and closure of their wounds with suturing, lateral skin release, split thickness skin grafting and muscle pedicle flap, where ever necessary. All the patients were followed up for a minimum of two years.
Statistical Analysis: Descriptive statistics and Fisher’s Exact test were used.
Results: Of the total thirty cases, ten were of grade I, seven were of grade II, three were of grade IIIA, seven were of grade IIIB and three were of grade IIIC. Dynamization was done in nine cases. The average time to union was 16.0 weeks in the grade I cases, it was 18.3 weeks in the grade II cases, it was 23.6 weeks in the grade III A cases, it was 28.4 weeks in the grade III B cases and it was 32 weeks in the grade III C cases. The mean time to union was 20.7 weeks. Infection occurred in 3 cases. Delayed unions were observed in 4 cases. A non union occurred in 1 case of type IIIC. A mal union was observed in 1 case of type IIIB. 1 case of grade IIIC had the compartmental syndrome. No case had any implant failure (nail / screw breakage), or deep vein thrombosis.
Conclusion: We conclude that the unreamed intramedullary nailing in cases of open fractures of the tibia, with an early soft tissue coverage, results in a faster soft tissue and bony healing, an easier soft tissue coverage, a better biomechanical stability and early rehabilitation and infection rates as comparable to those which are seen with other methods.
Open fracture; Tibia; Unreamed; Intramedullary nailing; Functional assessment
Improved medical therapies have increased survivorship rates for children with posterior fossa tumors; resultantly, morbidities associated with survivorship, such as executive function deficits, have become increasingly important to identify and address. Executive dysfunction can impact academic achievement as well as functional outcomes. We summarize studies describing executive functioning deficits in pediatric posterior fossa tumor survivors who received cranial radiation therapy and intervention studies that have targeted executive functioning deficits. Previous theoretical models describing the etiology of these deficits are reviewed, and a new, more comprehensive model is proposed. Future research should move toward incorporating neuroimaging, longitudinal designs, and multiple informants.
High-mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that is passively released from damaged and necrotic cells, and actively released from immune cells. In contrast, cytochrome c is released from mitochondria in apoptotic cells, and is considered a reliable biomarker of apoptosis. Thus, HMGB1 and cytochrome c may in part reflect the degree of necrosis and apoptosis present after traumatic brain injury (TBI), where both are felt to contribute to cell death and neurological morbidity. Ventricular cerebrospinal fluid (CSF) was obtained from children admitted to the intensive care unit (ICU) after TBI (n=37). CSF levels of HMGB1 and cytochrome c were determined at four time intervals (0–24 h, 25–48 h, 49–72 h, and>72 h after injury) using enzyme-linked immunosorbent assay (ELISA). Lumbar CSF from children without TBI served as controls (n=12). CSF HMGB1 levels were: control=1.78±0.29, 0–24 h=5.73±1.45, 25–48 h=5.16±1.73, 49–72 h=4.13±0.75,>72 h=3.80±0.90 ng/mL (mean±SEM). Peak HMGB1 levels were inversely and independently associated with favorable Glasgow Outcome Scale (GOS) scores at 6 mo (0.49 [0.24–0.97]; OR [5–95% CI]). CSF cytochrome c levels were: control=0.37±0.10, 0–24 h=0.69±0.15, 25–48 h=0.82±0.48, 49–72 h=1.52±1.08,>72 h=1.38±1.02 ng/mL (mean±SEM). Peak cytochrome c levels were independently associated with abusive head trauma (AHT; 24.29 [1.77–334.03]) and inversely and independently associated with favorable GOS scores (0.42 [0.18–0.99]). In conclusion, increased CSF levels of HMGB1 and cytochrome c were associated with poor outcome after TBI in infants and children. These data are also consistent with the designation of HMGB1 as a “danger signal.” Distinctly increased CSF cytochrome c levels in infants and children with AHT and poor outcome suggests that apoptosis may play an important role in this unique patient population.
abusive head trauma; child abuse; cytochrome c; high mobility group box 1
The crystallization of a putative SCP-x thiolase from M. smegmatis is described.
Thiolases are important in fatty-acid degradation and biosynthetic pathways. Analysis of the genomic sequence of Mycobacterium smegmatis suggests the presence of several putative thiolase genes. One of these genes appears to code for an SCP-x protein. Human SCP-x consists of an N-terminal domain (referred to as SCP2 thiolase) and a C-terminal domain (referred as sterol carrier protein 2). Here, the cloning, expression, purification and crystallization of this putative SCP-x protein from M. smegmatis are reported. The crystals diffracted X-rays to 2.5 Å resolution and belonged to the triclinic space group P1. Calculation of rotation functions using X-ray diffraction data suggests that the protein is likely to possess a hexameric oligomerization with 32 symmetry which has not been observed in the other six known classes of this enzyme.
Mycobacterium smegmatis; thiolases
A growing body of evidence indicates that oxidative stress plays a central role in the progression of chronic obstructive pulmonary disease (COPD). Chronic oxidative stress caused by cigarette smoke generates damage-associated molecular patterns (DAMPs), such as oxidatively or nitrosatively modified proteins and extracellular matrix fragments, which induce abnormal airway inflammation by activating innate and adaptive immune responses. Furthermore, oxidative stress–induced histone deacetylase 2 (HDAC2) inactivity is implicated in amplifying inflammatory responses and corticosteroid resistance in COPD. Oxidative stress also mediates disruption of innate immune defenses, which is associated with acute exacerbation of COPD. Host defense transcription factor Nuclear factor erythroid 2–related factor 2 (Nrf2) regulates a multifaceted cytoprotective response to counteract oxidative stress–induced pathological injuries. A decrease in Nrf2 signaling is associated with the progression of diseases. Recent evidence indicates that targeting Nrf2 can be a novel therapy to mitigate inflammation, improve innate antibacterial defenses, and restore corticosteroid responses in patients with COPD.
COPD; Nrf2; bacteria; exacerbation; therapeutics
Accurately reading the body language of others may be vital for navigating the social world, and this ability may be influenced by factors, such as our gender, personality characteristics and neurocognitive processes. This fMRI study examined the brain activation of 26 healthy individuals (14 women and 12 men) while they judged the action performed or the emotion felt by stick figure characters appearing in different postures. In both tasks, participants activated areas associated with visual representation of the body, motion processing and emotion recognition. Behaviorally, participants demonstrated greater ease in judging the physical actions of the characters compared to judging their emotional states, and participants showed more activation in areas associated with emotion processing in the emotion detection task, whereas they showed more activation in visual, spatial and action-related areas in the physical action task. Gender differences emerged in brain responses, such that men showed greater activation than women in the left dorsal premotor cortex in both tasks. Finally, participants higher in self-reported empathy demonstrated greater activation in areas associated with self-referential processing and emotion interpretation. These results suggest that empathy levels and sex of the participant may affect neural responses to emotional body language.
fMRI; body language; posture; emotion; gender; empathy
The underconnectivity theory of autism attributes the disorder to lower anatomical and functional systems connectivity between frontal and more posterior cortical processing. Here we review evidence for the theory and present a computational model of an executive functioning task (Tower of London) implementing the assumptions of underconnectivity. We make two modifications to a previous computational account of performance and brain activity in typical individuals in the Tower of London task (Newman et al., 2003): (1) the communication bandwidth between frontal and parietal areas was decreased and (2) the posterior centers were endowed with more executive capability (i.e., more autonomy, an adaptation is proposed to arise in response to the lowered frontal-posterior bandwidth). The autism model succeeds in matching the lower frontal-posterior functional connectivity (lower synchronization of activation) seen in fMRI data, as well as providing insight into behavioral response time results. The theory provides a unified account of how a neural dysfunction can produce a neural systems disorder and a psychological disorder with the widespread and diverse symptoms of autism.
autism; connectivity; underconnectivity; 4CAPS; computational model; fMRI
Tumor-associated antigen (TAA) subunit-based vaccines constitute promising tools for the anticancer immunotherapy. Given the weak antigenic nature of most TAAs, however, the efficacy of TAA-based vaccines requires adjuvants exerting potent immunostimulatory functions. Co-stimulatory members of the tumor necrosis factor ligand (TNFL) family may be used in this sense due to their pleiotropic and robust effects on cells of innate, adaptive and regulatory immune responses.
anticancer immunity; cancer vaccines; CD137; lung cancer; SA-4-1BBL; survivin
Intracranial extra-axial cavernous angiomas are rare lesions. We report a rare case of extra-axial cavernous angioma in the cerebellopontine angle (CPA) in a 50-year-old male, who presented with lower cranial nerve palsy and gait ataxia. Computed tomography (CT) scan of the brain showed a hyperdense lesion in the left cerebellopontine angle. The lesion was totally excised by the retrosigmoid approach and a pathological examination confirmed the lesion to be a cavernous angioma. Following surgery, the lower cranial nerve palsy recovered significantly.
Cavernous angioma; cerebellopontine angle; cavernous hemangioma
Malaria presents a diagnostic challenge in areas where both Plasmodium falciparum and P.vivax are co-endemic. Bivalent Rapid Diagnostic tests (RDTs) showed promise as diagnostic tools for P.falciparum and P.vivax. To assist national malaria control programme in the selection of RDTs, commercially available seven malaria RDTs were evaluated in terms of their performance with special reference to heat stability.
This study was undertaken in four forested districts of central India (July, 2011– March, 2012). All RDTs were tested simultaneously in field along with microscopy as gold standard. These RDTs were stored in their original packing at 25°C before transport to the field or they were stored at 35°C and 45°C upto 100 days for testing the performance of RDTs at high temperature. In all 2841 patients with fever were screened for malaria of which 26% were positive for P.falciparum, and 17% for P.vivax. The highest sensitivity of any RDT for P.falciparum was 98% (95% CI; 95.9–98.8) and lowest sensitivity was 76% (95% CI; 71.7–79.6). For P.vivax highest and lowest sensitivity for any RDT was 80% (95% CI; 94.9 - 83.9) and 20% (95% CI; 15.6–24.5) respectively. Heat stability experiments showed that most RDTs for P.falciparum showed high sensitivity at 45°C upto 90 days. While for P.vivax only two RDTs maintained good sensitivity upto day 90 when compared with RDTs kept at room temperature. Agreement between observers was excellent for positive and negative readings for both P.falciparum and P.vivax (Kappa >0.6–0.9).
This is first field evaluation of RDTs regarding their temperature stability. Although RDTs are useful as diagnostic tool for P.falciparum and P.vivax even at high temperature, the quality of RDTs should be regulated and monitored more closely.
Eight fermentative bacterial strains were isolated from mixed enrichment cultures of a composite soil sample collected at 1.34 km depth from the former Homestake gold mine in Lead, SD, USA. Phylogenetic analysis of their 16S rRNA gene sequences revealed that these isolates were affiliated with the phylum Firmicutes belonging to genera Bacillus and Clostridium. Batch fermentation studies demonstrated that isolates had the ability to ferment glucose, xylose, or glycerol to industrially valuable products such as ethanol and 1,3-propanediol (PDO). Ethanol was detected as the major fermentation end product in glucose-fermenting cultures at pH 10 with yields of 0.205–0.304 g of ethanol/g of glucose. While a xylose-fermenting strain yielded 0.189 g of ethanol/g of xylose and 0.585 g of acetic acid/g of xylose at the end of fermentation. At pH 7, glycerol-fermenting isolates produced PDO (0.323–0.458 g of PDO/g of glycerol) and ethanol (0.284–0.350 g of ethanol/g of glycerol) as major end products while acetic acid and succinic acid were identified as minor by-products in fermentation broths. These results suggest that the deep biosphere of the former Homestake gold mine harbors bacterial strains which could be used in bio-based production of ethanol and PDO.
bioenergy; bioethanol; biofuels; fermentation; gold mine; 1,3-propanediol
Molecular characterization of subsurface microbial communities in the former Homestake gold mine, South Dakota, was carried out by 16S rDNA sequence analysis using a water sample and a weathered soil–like sample. Geochemical analyses indicated that both samples were high in sulfur, rich in nitrogen and salt, but with significantly different metal concentrations. Microbial diversity comparisons unexpectedly revealed three distinct operational taxonomic units (OTUs) belonging to the archaeal phylum Thaumarchaeota typically identified from marine environments, and one OTU to a potentially novel phylum that falls sister to Thaumarchaeota. To our knowledge this is only the second report of Thaumarchaeota in a terrestrial environment. The majority of the clones from Archaea sequence libraries fell into two closely related OTUs and grouped most closely to an ammonia–oxidizing, carbon–fixing and halophilic thaumarchaeote genus, Nitrosopumilus. The two samples showed neither Euryarchaeota nor Crenarchaeota members that were often identified from other subsurface terrestrial ecosystems. Bacteria OTUs containing the highest percentage of sequences were related to sulfur-oxidizing bacteria of the orders Chromatiales and Thiotrichales. Community members of Bacteria from individual Homestake ecosystems were heterogeneous and distinctive to each community with unique phylotypes identified within each sample.
16S rDNA; Thaumarchaeota; phylogenetic microbial diversity; Homestake gold mine; extremophiles
The population explosion and unintended pregnancies resulting in elective abortions continue to impose major public health issues. This calls for a better method of contraception. Immunocontraception has been proposed as a valuable alternative that can fulfill most, if not all, of the properties of an ideal contraceptive. There are several targets that are being explored for contraceptive vaccine development. Leukemia inhibitory factor (LIF), a member of interleukin-6 family, is required for embryo development and successful blastocyst implantation in several mammalian species. The present study was conducted to examine if LIF can be a target for the development of a birth control vaccine. Three sequences from LIF and two sequences from LIF-receptor (LIF-R) that span the regions involved in ligand-receptor binding were delineated, and peptides were synthesized based upon these sequences. Antibodies raised against these five peptides reduced LIF bioactivity in the in vitro culture assay using BA/F3 mLIF-R-mpg130 cells. Vaccines were prepared by conjugating these peptides to various carrier proteins. Immunization of female mice with these peptide vaccines induced a long-lasting, circulating as well as local antibody response in various parts of the genital tract, and resulted in a significant (p≤0.05) inhibition in fertility in all the three trials; the LIF-R peptide vaccines proved to be a better vaccine target. The data indicate that LIF/LIF-R is an excellent target for the development of a birth control vaccine. This is the first study, to our knowledge, that examined LIF/LIF-R as a target for immunocontraception. The findings of this study can be easily translated to humans since LIF/LIF-R is also important for implantation and pregnancy in women.
leukemia inhibitory factor; contraceptive vaccine; mucosal immunity; genital tract immunity; peptide vaccine; contraception; implantation; pregnancy
Alterations in interregional neural connectivity have been suggested as a signature of the pathobiology of autism. There have been many reports of functional and anatomical connectivity being altered while individuals with autism are engaged in complex cognitive and social tasks. Although disrupted instantaneous correlation between cortical regions observed from functional MRI is considered to be an explanatory model for autism, the causal influence of a brain area on another (effective connectivity) is a vital link missing in these studies. The current study focuses on addressing this in an fMRI study of Theory-of-Mind (ToM) in 15 high-functioning adolescents and adults with autism and 15 typically developing control participants. Participants viewed a series of comic strip vignettes in the MRI scanner and were asked to choose the most logical end to the story from three alternatives, separately for trials involving physical and intentional causality. The mean time series, extracted from 18 activated regions of interest, were processed using a multivariate autoregressive model (MVAR) to obtain the causality matrices for each of the 30 participants. These causal connectivity weights, along with assessment scores, functional connectivity values, and fractional anisotropy obtained from DTI data for each participant, were submitted to a recursive cluster elimination based support vector machine classifier to determine the accuracy with which the classifier can predict a novel participant's group membership (autism or control). We found a maximum classification accuracy of 95.9% with 19 features which had the highest discriminative ability between the groups. All of the 19 features were effective connectivity paths, indicating that causal information may be critical in discriminating between autism and control groups. These effective connectivity paths were also found to be significantly greater in controls as compared to ASD participants and consisted predominantly of outputs from the fusiform face area and middle temporal gyrus indicating impaired connectivity in ASD participants, particularly in the social brain areas. These findings collectively point toward the fact that alterations in causal connectivity in the brain in ASD could serve as a potential non-invasive neuroimaging signature for autism.
autism; effective connectivity; fMRI; classification; machine learning; theory-of-mind
Symphysodontella madhusoodananii Manju & Rajesh, sp. nov. an epiphytic pendant moss, with flagellate branches and long acuminate leaves with two short costa is described and illustrated from the tropical wet evergreen forests of the Western Ghats of India.
Symphysodontella madhusoodananii; Pterobryaceae; Moss; Western Ghats; New Amarambalam; Kerala; India
The default mode network (DMN) is a collection of brain areas found to be consistently deactivated during task performance. Previous neuroimaging studies of resting state have revealed reduced task-related deactivation of this network in autism. We investigated the DMN in 13 high-functioning adults with autism spectrum disorders (ASD) and 14 typically developing control participants during three fMRI studies (two language tasks and a Theory-of-Mind (ToM) task). Each study had separate blocks of fixation/resting baseline. The data from the task blocks and fixation blocks were collated to examine deactivation and functional connectivity. Deficits in the deactivation of the DMN in individuals with ASD were specific only to the ToM task, with no group differences in deactivation during the language tasks or a combined language and self-other discrimination task. During rest blocks following the ToM task, the ASD group showed less deactivation than the control group in a number of DMN regions, including medial prefrontal cortex (MPFC), anterior cingulate cortex, and posterior cingulate gyrus/precuneus. In addition, we found weaker functional connectivity of the MPFC in individuals with ASD compared to controls. Furthermore, we were able to reliably classify participants into ASD or typically developing control groups based on both the whole-brain and seed-based connectivity patterns with accuracy up to 96.3%. These findings indicate that deactivation and connectivity of the DMN were altered in individuals with ASD. In addition, these findings suggest that the deficits in DMN connectivity could be a neural signature that can be used for classifying an individual as belonging to the ASD group.
Subunit vaccines containing universal tumor associated antigens (TAAs) present an attractive treatment modality for cancer primarily due to their safety and potential to generate long-term immunological responses that can safeguard against recurrences. However, TAA-based subunit vaccines require potent adjuvants for therapeutic efficacy. Using a novel form of the 4-1BBL costimulatory molecule, SA-4-1BBL, as the adjuvant of choice, we previously demonstrated that a single vaccination with survivin (SVN) as a bona fide self TAA was effective in eradicating weakly immunogenic 3LL tumors in >70% of C57BL/6 mice. The present study was designed to i) assess the therapeutic efficacy of a prime-boost vaccination and ii) investigate the mechanistic basis of vaccine efficacy. Our data shows that a prime-boost vaccination strategy was effective in eradicating 3LL lung carcinoma in 100% of mice. The vaccine efficacy was correlated with increased percentages of CD8+ T cells expressing IFN-γ as well as potent killing responses of both CD8+ T and NK cells in the absence of detectable antibodies to ssDNA as a sign of autoimmunity. Antibody depletion of CD8+ T cells one day before vaccination completely abrogated therapeutic efficacy, whereas depletion of CD4+ T cells had no effect. Importantly, NK cell depletion had a moderate (∼50% reduction), but significant (p<0.05) effect on vaccine efficacy. Taken together, these results shed light on the mechanistic basis of the SA-4-1BBL/SVN subunit vaccine formulation in a lung carcinoma model and demonstrate the robust therapeutic efficacy of the prime-boost immunization strategy with important clinical implications.
Neoadjuvant chemotherapy (NACT) is an essential part of multi-disciplinary management of locally advanced breast cancer (LABC). In this study, we aimed at evaluating the role of Tc99m-Sestamibi scinti-mammography in assessing response to NACT in patients with LABC.
Materials and Methods:
A total of 42 patients of histologically proven LABC were enrolled in this prospective study. Imaging was performed according to pre-defined protocol at 10 min and 4 h after injection of tracer before the start of chemotherapy, 48 h after start of chemotherapy and at the end of chemotherapy. Quantitative parameters were obtained by calculating the ratio of activity in a region of interest (ROI) drawn over the tumor and the same sized ROI drawn in corresponding location in contra lateral breast.
At the end of chemotherapy, 6 patients achieved complete response, 25 achieved partial response, 11 had stable disease. Various retention indices calculated at baseline, 48 h after first cycle of NACT, and at the end of chemotherapy showed statistically significant difference in responders and non-responders. By using 84.05 as cut-off point for retention index (RI) of tumor calculated 48 h after first cycle of NACT (RI 2) the positive predictive value and negative predictive value, were found to be 41.9% and 72.7% respectively in differentiating responders from non-responders.
Early response assessment in patients with LABC to NACT with Tc99m-Sestamibi scintimammography is feasible and if confirmed by further studies can find routine clinical application in differentiating responders from non-responders.
Locally advanced breast cancer; response evaluation; scintimammography; Tc99m-Sestamibi
Spinal epidural angiolipomas are rare, benign tumors composed of mature lipocytes admixed with abnormal blood vessels. Only 128 cases of spinal epidural angiolipomas have been reported in literature till now. Spinal angiolipomas are predominantly located in the mid-thoracic region. We report a case of dorsal epidural angiolipoma in a 56-year-old male who presented with paraparesis and was diagnosed to have D4-5 epidural angiolipoma. Total surgical excision of the epidural angiolipoma was done and his paraparesis gradually improved.
Angiolipoma; spinal epidural tumor; spinal tumor
To study the effect of antiretroviral therapy (ART) on clinical, immunologic, and nutritional progression of disease in human immunodeficiency virus (HIV)-infected children for 1 year.
Materials and Methods:
The study included 54 children aged 1.5–15 years who registered at the ART center, Surat, from August 2007 to August 2009. During the study period, the children were followed-up at 6 monthly intervals up to 1 year after starting ART. World Health Organization (WHO) clinical staging and CD4 cell count as per national guidelines, and nutritional status were used to measure clinical and immunologic progression of disease up to 1 year.
Out of 54 children, mother-to-child transmission was reported in 96.2% children; for 74% of the children, both parents were HIV positive. All the children were classified according to WHO clinical staging into 4 stages and as per CD4 cell count (%), followed up at 6 and 12 months and the benefits with ART reported. At 12 months follow-up, 15% of the study group children had died. Both mean CD4 count and a relative percentage showed significant increase (P < 0.01) in the study group 1 year after ART.
The present study reports benefits of ART in terms of clinical and immunologic progression of disease, nutritional status of HIV-infected children after 1 year of ART.
ART; CD4 cell count; HIV-positive children; nutrition; WHO clinical staging