Rapid Nanophotonics Assay for Head and Neck Cancer Diagnosis.

Efficient and timely diagnosis of head and neck squamous cell carcinoma (HNSCC) is a critical challenge, particularly in low and middle income countries. These regions, which are expected to witness a drastic increase in HNSCC rates, are ill-prepared to handle the diagnostic burden due to limited resources, especially the low ratio of pathologists per population, resulting in delayed diagnosis and treatment. Here, we demonstrate the potential of an alternative diagnostic method as a low-cost, resource-efficient alternative to histopathological analysis. Our novel technology employs unique surface-enhanced Raman scattering (SERS) "nanorattles" targeting cytokeratin nucleic acid biomarkers specific for HNSCC. In this first study using SERS diagnostics for head and neck cancers, we tested the diagnostic accuracy of our assay using patient tissue samples. In a blinded trial, our technique demonstrated a sensitivity of 100% and specificity of 89%, supporting its use as a useful alternative to histopathological diagnosis. The implications of our method are vast and significant in the setting of global health. Our method can provide a rapid diagnosis, allowing for earlier treatment before the onset of distant metastases. In comparison to histopathology, which can take several months in remote limited-resources regions, our method provides a diagnosis within a few hours.

Author Correction: Rapid Nanophotonics Assay for Head and Neck Cancer Diagnosis.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Squamous Cell Carcinoma DNA Detection Using Ultrabright SERS Nanorattles and Magnetic Beads for Head and Neck Cancer Molecular Diagnostics.

A rise in head and neck cancers in low and middle countries over recent years has prompted the need for low-cost, resource-efficient diagnostic technologies. Standard diagnosis with histopathology is often not feasible due to the low number of trained pathologists in these regions, resulting in delayed diagnosis and treatment. This study presents an alternative diagnostic method to standard histopathology. We developed a surface enhanced raman scattering (SERS) based method to distinguish squamous cell carcinoma from other cell lines. Using a "sandwich" method employing ultrabright SERA nanorattles and magnetic beads, we directly targeted specific nucleic acid markers of squamous cells. Our method was able to detect the presence of squamous cells with high sensitivity and specificity, supporting its potential for use as a diagnostic tool in head and neck fine needle aspirations (FNA).

Hemophilus influenzae meningitis and septicaemia in a 14-month-old child after primary immunisation.

We report a 14-month-male child, who developed Hemophilus influenzae meningitis after three primary doses of the vaccine. The child presented with fever and seizures. H. influenzae was isolated from both cerebrospinal fluid (CSF) and blood. The child also had features of septicaemia. Procalcitonin (104 ng/ml) and C-reactive protein (CRP--42.6 mg/dl) were high. Appropriate antibiotics were given. The child made an uneventful recovery. This case highlights vaccine failure, especially after primary immunisation alone.

Applications of pectinases in the commercial sector: a review.

Pectinases are one of the upcoming enzymes of fruit and textile industries. These enzymes break down complex polysaccharides of plant tissues into simpler molecules like galacturonic acids. The role of acidic pectinases in bringing down the cloudiness and bitterness of fruit juices is well established. Recently, there has been a good number of reports on the application of alkaline pectinases in the textile industry for the retting and degumming of fiber crops, production of good quality paper, fermentation of coffee and tea, oil extractions and treatment of pectic waste water. This review discusses various types of pectinases and their applications in the commercial sector.

Inflammatory bowel disease.

Till about 3 decades ago, inflammatory bowel disease (IBD) was considered as non-existent in our country. However, since that time several reports of IBD, mainly ulcerative colitis have been published. More recently, Crohn's disease is also being reported from the country. This trend of UC appearing first in a population followed by CD also appears to be true in other developing nations. A substantial increase in the rates of CD over UC in the last few decades is reported from developed nations as well. Of the other epidemiological factors, an increased risk of CD and lower risk of UC in smokers is established in adults. However, it appears that smoking increases the risk of IBD in children. The etiology of IBD remains elusive. Within the triad of genetics, immunity and antigen responsible for the development of IBD, maximum advances have been made in the field of immune aberrations and this is being exploited to treat the disease. It is well established that IBD results from a disordered immune system in the gut, in response to an unidentified antigen in a predisposed individual. The immune response is enhanced and revolves around antigen-presenting cells, CD 4 T-lymphocytes and tumor necrosis factor alpha. CD results from an enhanced Th1 activity. The pathogenesis of UC is less clear but appears to be humoral. Advances in diagnostics include the availability of serology, ultrasound and nuclear scans, none of which have been tried in our setting where infectious diseases and tuberculosis is rampant. Growth failure and the importance of nutrition in IBD, especially CD, cannot be underemphasized. In many situations nutritional interventions have been used solely as a form of therapy for CD. Newer steroid molecules with minimal systemic effects are also being considered. Other treatment options highlighted are the use of immunosuppressive agents, biologic agents and role of surgery.

A pilot study of posttraumatic stress and nonadherence in pediatric liver transplant recipients.

BACKGROUND: Symptoms of posttraumatic stress disorder (PTSD) were described in survivors of life-threatening diseases, the trauma being the experiences associated with the disease or its treatment. Their prevalence in liver transplant recipients is unknown. Based on clinical observations, we hypothesize that a significant proportion of pediatric liver transplant recipients suffers from PTSD symptoms. We further hypothesize that nonadherence (noncompliance) to medical management may, in some cases, be associated with these symptoms. Traumatized patients, according to this hypothesis, will avoid taking their medications, because these serve as painful reminders of the disease. OBJECTIVES: To determine the prevalence of PTSD symptoms in a sample of pediatric liver transplant recipients. To determine whether symptoms of PTSD are associated with nonadherence in these patients. To describe the clinical presentation of PTSD and the management of severe nonadherence in patients who suffer from this disorder. METHODS: Nineteen pediatric liver transplant recipients and their caretakers were interviewed, using the UCLA Post Traumatic Stress Disorder Reaction Index (PTSRI). Data were obtained on a few demographic parameters and perception of disease threat. Adherence was evaluated by 2 methods: 1) a clinician panel (taking into account the clinical sequelae of severe nonadherence); and 2) computation of the standard deviations (SDs) of consecutive determinations of blood levels of Tacrolimus (a higher SD means higher variability between individual measures and is therefore an indicator of nonadherence). As an illustration of the general phenomenon, we describe 3 cases of liver transplant recipients who were nonadherent and who suffered from PTSD. RESULTS: Six of 19 patients had positive scores on all 3 components of the PTSRI (PTSD patients). Three of these, and none of the others, were considered significantly nonadherent by the panel. Therefore, nonadherence was significantly associated with the existence of symptoms from all 3 domains of PTSD (Fisher's exact test) in our sample. In particular, a high avoidance score on the PTSRI was highly correlated with panel-determined nonadherence. Further, SD of medication levels were significantly higher in PTSD patients, compared with the rest of our sample. No significant differences were found in perception of disease threat or demographic variables between PTSD patients and the rest of our sample. The 3 cases that we describe became adherent to their medications when symptoms of PTSD subsided during the course of therapy. CONCLUSIONS: Clinically significant nonadherence, determined by 2 different methods, was associated with the full spectrum of PTSD symptoms in this sample. It was especially associated with a high avoidance score, which suggests that avoidance of reminders of the disease (eg, medications) may be a mechanism of nonadherence. Screening for and management of these symptoms, therefore, may improve adherence. This novel concept may be applicable to other patient populations. However, more data are needed before any definite conclusions can be drawn.

Induction of cytotoxic T-cell responses following oral immunization with synthetic peptides encapsulated in PLG microparticles.

CTL responses play a critical role in clearing viral infections. We have investigated the potential of poly(lactide-co-glycolide) (PLG) microparticles as an oral delivery system for peptides representing CTL epitopes from measles virus nucleoprotein. Oral administration of CTL epitopes encapsulated in 50:50 PLG microparticles, resulted in vivo priming of splenic peptide-specific CTL responses. However, the observed CTL lysis was low and cofeeding of encapsulated peptide with cholera toxin as a mucosal adjuvant did not result in any significant enhancement of the observed CTL responses. The pronounced immunostimulatory effect of microparticles, combined with their excellent tissue compatibility and biodegradability makes them a valuable delivery system for synthetic peptide immunogens. However, further work is needed to improve their efficiency via the oral route.

Management of heel pain syndrome with acetic acid iontophoresis.

This study was undertaken to determine the effectiveness of acetic acid iontophoresis in the treatment of heel pain. Thirty-five patients with chronic heel pain were treated with acetic acid iontophoresis over a 4-year period. Ninety-four percent of patients had complete or substantial relief of heel pain after an average of 5.7 sessions of acetic acid iontophoresis over an average period of 2.8 weeks. Heel pain levels were rated from 0 to 10, with 10 representing the most severe pain. Heel pain prior to iontophoresis treatment received an average rating of 7.5; by the end of therapy, the average rating had decreased to 1.8. At an average follow-up time of 27 months, heel pain levels averaged 0.64, indicating continued reduction in heel pain. Ninety-four percent of participants said that they would recommend acetic acid iontophoresis to someone with similar heel pain.

Long-term follow-up of heel spur surgery. A 10-year retrospective study.

A comparative retrospective study of 48 open heel spur surgeries and 20 endoscopic plantar fasciotomies was conducted involving 59 patients over a 10-year period. There was a significant reduction in heel pain at the time of follow-up (average, 3 years) for both groups. Overall, 85% of procedures were associated with patient satisfaction with the results, and patients said that they would recommend heel spur surgery for relief of severe heel pain in 94% of cases. Factors influencing the postoperative outcome, such as duration of preoperative symptoms, extent of conservative care, and obesity, are discussed.

CTL responses induced by a single immunization with peptide encapsulated in biodegradable microparticles.

A synthetic peptide representing a measles virus (MV) cytotoxic T cell epitope (CTL) when encapsulated in poly (D,L-lactide co-glycolide) (PLG) 50:50 microparticles induced a strong CTL response after a single intraperitoneal immunization of mice which was greater than that following administration of the peptide in Freund's complete adjuvant. A 100 micrograms dose of encapsulated peptide was shown to be more effective for CTL priming than 50 and 25 micrograms doses. A vaccine formulation prepared by simply mixing empty 50:50 PLG microparticles with the peptide resulted in the induction of CTL responses comparable to those induced by the encapsulated peptide. Moreover, a CTL response against MV-infected target cells was observed. These findings highlight the potential immunostimulatory effect of PLG microparticles for the induction of MV and peptide-specific CTL responses.

Effect of halofuginone (Stenorol) on Chukar partridge (Alectoris chukar).

This study was conducted to assess the effect of the coccidiostat halofuginone (Stenorol) on growth, feed consumption, and survival of Chukar partridge. Halofuginone was fed to three replicates (14 chicks per replicate) of chukar chicks from 2 to 7 d of age at levels of 0, 1.5, 3.0, 6.0 and 12 ppm. Mortality from 2 to 7 d was 0, 0, 0, 11, and 21 birds, respectively, by treatment. Seven-day body weight showed a significant linear decrease with increasing halofuginone level (P < 0.01). On the 7th d, replicates receiving 6.0 and 12.0 ppm halofuginone were transferred to unmedicated feed for the remainder of the test due to excessive mortality. The other groups were continued until 6 wk of age. At 6 wk, chicks fed 6 or 12 ppm halofuginone from 2 to 7 d and then unmedicated feed did not differ in body weight from those fed the unmedicated control diet. A significant difference in mortality was not observed among the other three treatment groups to 6 wk of age. A linear depression in 3-, 4-, 5-, and 6-wk body weight with increasing halofuginone level was observed within the first three treatment levels (P < 0.05). It was concluded that 1.5 ppm halofuginone depressed growth of young chukars and that 6 ppm resulted in increased mortality.

Mucosal immunization with a measles virus CTL epitope encapsulated in biodegradable PLG microparticles.

The immunogenicity of a cytotoxic T cell epitope (CTL) representing residues 52-60 from measles virus (MV) nucleoprotein, encapsulated in poly(lactide-co-glycolide) (PLG) microparticles was evaluated after mucosal immunization. After intranasal administration of the encapsulated CTL epitope linked at the carboxyl terminus of two copies of a T-helper epitope (TT-NP6), peptide-specific and MV-specific CTL responses were detected in splenocytes. However, these responses were lower than the responses observed when the TT-NP6 peptide was administered intranasally in saline or using CTB as an adjuvant. Intranasal coadministration of the encapsulated TT-NP6 peptide with CTB did not result in any significant potentiation of the CTL responses. The effectiveness of biodegradable PLG microparticles for mucosal delivery of CTL epitopes, combined with their excellent tissue compatibility and biodegradability suggests that they represent a valuable delivery system for synthetic immunogens. However, further work is needed to define the requirements for effective absorption by the nasal epithelium.

The 'small spleen' in malaria.

A cardinal feature of malaria, splenomegaly, is usually absent in adult patients who have already suffered from falciparum malaria or who are natives of an endemic falciparum zone. This is an attribute of the past episode of clinical or sub-clinical malaria which usually results in regression of the splenic size to below-normal. An ultrasonographic evaluation of spleens was done in 90 healthy adult males, who had suffered from vivax (n = 28) or falciparum (n = 25) malaria in the past, except the controls (n = 22) and natives from an endemic falciparum area (n = 15) who never suffered from malaria. Their ultrasonographic details of spleens, including the size, were compared. Besides other conspicuous differences in the ultrasonographic picture, spleen size was found significantly decreased (p < 0.01) in the group who had been affected by P. falciparum malaria; the smallest measured 7.8 cms. In P. vivax group the decrease was not significant (p < 0.1), but was highly significant in inhabitants of endemic falciparum region (p < 0.001). The present study establishes the 'Small Spleen' and looks at echotexture pattern variations thereof for the first time.

Ankle arthroscopy: follow-up study of 33 ankles--effect of physical therapy and obesity.

A retrospective analysis was conducted of 32 patients (33 ankles) who had undergone surgical ankle arthroscopy for chronic ankle pain that was recalcitrant to conservative treatment. All patients were examined clinically and completed a written questionnaire. Intraoperative ankle arthroscopy showed hypertrophic synovitis, adhesive bands, chondral bands with synovitis, osteophytes, and abnormalities in the talar dome. Results of treatment after an average follow-up time of 1.4 years (range: 0.33 to 12.5 years) showed ankle scores of 15 excellent, 11 good, 5 fair, and 2 poor. Obesity was significantly related to the outcomes of arthroscopy procedures. Obese patients were more likely to be rated as fair or poor, while nonobese patients were significantly more likely to be rated excellent or good. Those patients who received physical therapy postoperatively for one or more months had significantly better ankle ratings than those who did not elect to have physical therapy.

Biodegradable microparticles as a delivery system for measles virus cytotoxic T cell epitopes.

Cytotoxic T-cell (CTL) responses are likely to be important for the clearance of a measles virus (MV) infection. To induce CTL responses. replicating vectors have generally been used but the use of such vectors in humans mav be problematic, and immunization with synthetic peptides may be more appropriate. We have investigated the potential of poly(lactide-co-glycolide)(PLG) microparticles as a delivery system for a CTL epitope representing residues 51-59 from MV nucleoprotein. After a single intraperitoneal injection in saline of the encapsulated epitope, CTL responses to the homologous peptide and MV were detected over a period of 4 months. Responses reached a maximum 30 days after priming and were maintained at high levels for 120 days. These responses were higher than those observed when the CTL epitope was administered in saline or as an emulsion in Incomplete Freund's Adjuvant. The pronounced immunostimulatory effect of microparticles, combined with their excellent tissue compatibility and biodegradability suggests that they represent a valuable delivery system for synthetic peptide immunogens.

Induction of measles virus-specific cytotoxic T-cell responses after intranasal immunization with synthetic peptides.

We have investigated the structural requirements for the induction of cytotoxic T-cell responses (CTL) in vivo after intranasal immunization with an immunodominant CTL epitope from the nucleoprotein of measles virus (MV). For the induction of CTL responses, covalent linkage of the CTL epitope to a helper T-cell epitope was required and the orientation of the epitopes influenced the immunogenicity of the CTL epitope. The presence of two copies as compared with one copy of a T-helper epitope, rendered the CTL epitope more immunogenic and resulted in the in vivo induction of MV-specific CTLs without the need for an adjuvant. The role of CTL responses to this epitope in protection after intranasal administration was evaluated in a mouse model against challenge with a neuroadapted strain of MV. Although a decreased mortality in the peptide immunized compared with that in unimmunized mice was observed, the protection achieved was not significant. These findings highlight the importance of the rational design of synthetic immunogens for the induction of CTL responses and the potential of the intranasal route for immunization.