Carbohydrate fatty acid monosulphate ester is a potent adjuvant for low-dose seasonal influenza vaccines.

There is still a need for a better and affordable seasonal influenza vaccine and the use of an adjuvant could solve both issues. Therefore, immunogenicity of a combination of low dose of 1/5TH (3 µg of HA) a licensed seasonal flu vaccine with the novel carbohydrate fatty acid monosulfate ester (CMS)-based adjuvant was investigated in ferrets and safety in rabbits. Without CMS, hemagglutination inhibition (HI) antibody titers ranged from ≤5 to 26 three weeks post immunization 1 (PV-1) and from 7 to 134 post-immunization 2 (PV-2) in ferrets. Virus neutralizing (VN) antibody titers ranged from 20 to 37 PV-1 and from 21 to 148 PV-2. CMS caused 10 to 111- fold increase in HI titers and 3 to 58- fold increase in VN titers PV-1 and PV-2, depending on influenza strain and dose of adjuvant. Eight mg of CMS generated significantly higher antibody titers than 1 or 4 mg, while 1 and 4 mg induced similar responses. Three µg of HA plus 4 mg of CMS was considered the highest human dose and safety of two-fold this dose was determined in acute and repeated-dose toxicity studies in rabbits conducted according to OECD GLP guidelines. The test item did not elicit any clinical signs, local reactions, effect on body weight, effect on urine parameters, effect on blood biochemistry, or gross pathological changes. In blood, increased numbers of neutrophils, lymphocytes and/or monocytes were noted and in iliac lymph nodes, increased cellularity of macrophages of minimal to mild degree were observed. In both ferrets and rabbits, body temperature increased with increasing dose of CMS to a maximum of 1 ˚C during the first day post-immunization, which returned to normal values during the second day. In the local tolerance study, histopathology of the site of injection at 7 days PV-1 revealed minimal, mild or moderate inflammation in 5, 8 and 5 animals, respectively. In the repeated-dose study and 21 days PV-3, minimal, mild or moderate inflammation was observed in 15, 18 and 3 animals, respectively. We concluded that the data show CMS is a potent and safe adjuvant ready for further clinical development of a seasonal influenza vaccine and combines high immunogenicity with possible antigen-sparing capacity.

Electrode impedances in children with cochlear implants: Comparison between intra-operative Switch ON and post-operative Switch ON.

INTRODUCTION: Intra-operative Switch ON (IOSO) is a novel clinical approach of activating the cochlear implant during the surgery adopted at our cochlear implantation center.We compared the electrode impedances in two conditions of Switch ON of cochlear implants; IOSO and post-operative Switch ON (POSO, 21st day of surgery). METHODS: Electrode impedances of 185 cochlear implants, 93 of whom received IOSO and 92 POSO, recorded over 10 years were analyzed retrospectively. RESULTS: Electrode impedances of IOSO group were significantly lower than POSO group at Switch ON and 3rd, 6th, 9th, and 12th months post cochlear implantation. In IOSO group, 3rd month's electrode impedances were high when compared to electrode impedances at Switch ON. Beyond the 3rd months, electrode impedance remained unchanged. In POSO group, there were no significant differences in electrode impedances between any measurement schedule. CONCLUSIONS: To our knowledge, this is the first study to investigate in detail the electrode impedances of the two above-said conditions of Switch ON in the process of cochlear implantation. This study concludes that timing of CI Switch ON has a significant effect on the electrode impedances. These results may affect the choice of cochlear implant Switch ON timing.

Extended-duration thromboprophylaxis after ventral hernia repair: a risk model to predict venous thrombotic events after hospital discharge.

BACKGROUND: Venous thromboembolism (VTE) is a major source of morbidity and mortality after ventral hernia surgery, but the risk of VTE after discharge has not been reported. STUDY DESIGN: Data from the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) were used to investigate the risk of post-discharge VTE. Current procedural terminology (CPT) codes identified all reported patients who underwent ventral hernia repair from 2011 to 2017. We created a multivariable regression model for post-discharge VTE, using the 2011-2016 dataset to develop the model and 2017 as a validation set. The prediction model was used to create a risk calculator as a mobile application. RESULTS: The rate of VTE after surgery was 0.62% (878 of 141,065) with 48% occurring after discharge from the hospital. The final predictor model consisted of eight variables: age > 60 years, male sex, body mass index (BMI) ≥ 35 kg/m2), operative time > 2 h, concurrent panniculectomy, post-operative hospitalization > 1 day, presence of bleeding disorder, and emergency operation. The model had good calibration and discrimination (Hosmer-Lemeshow goodness-of-fit test, p = 0.71; c-statistic = 0.71). Threshold analysis showed a strategy of extended-duration thromboprophylaxis was optimized when the risk of post-discharge VTE was > 0.3%. CONCLUSION: Forty-eight percent of VTEs after ventral hernia repair occur after discharge, particularly in older, male, obese patients undergoing longer and complex operations that require hospitalization > 1 day. Post-discharge thromboprophylaxis should be considered in these patients, particularly when risk of VTE exceeds 0.3%.

Evaluation of Temporal Processing Abilities in Competing Noise.

Temporal processing is critical to a wide variety of everyday listening tasks, including speech perception. Although the importance of signal to noise ratio (SNR) is well documented in speech perception experiments, it is less explored in temporal processing experiments. The present study examined the effect of SNR on temporal processing abilities using Gap Detection Threshold (GDT) in children and adults. The study included a total of 45 subjects, where in, 25 children (Group-1) and 20 adults (Group-2) with pure-tone thresholds ranging from 0 to 25 dB HL at frequency range 250-8000 Hz. The GDT was measured at presentation level 50 dBSL. All the measurements were performed in 5 different conditions: 'Quiet', ' + 10 dB SNR', ' + 5 dB SNR', ' + 0 dB SNR' and ' - 5 dB SNR'. Gap Detection Thresholds are significantly higher from + 10 to - 5 dB SNR when compared to quiet condition in young-adults and all sub-groups of children, whereas at + 10 dB SNR, thresholds were not significantly different from quiet condition in young-adults and all sub-groups of children except for sub-group A of children, and were significantly different for all the five conditions. It was revealed that, as the signal to noise ratio (SNR) was decreased from + 10 dB SNR to 0 dB SNR there was a significant increase in Gap Detection Thresholds. There was a significant increase in Gap Detection Thresholds from + 10 dB SNR to - 5 dB SNR in both children and adults. The results also suggest that the performance on temporal processing task in the presence of background noise achieves young-adult like pattern by the age of 10-11 years. Background noise affect temporal processing in both children and young-adults. Background noise impairs temporal processing in children more than the adults, which could be because of poor temporal resolving abilities in children.

Auditory, Speech and Language Development in Cochlear Implant Children: A One Year Longitudinal Study.

The advent of Cochlear Implants (CI) has bought with it, the goal of spoken language performance for severe-profound sensori-neural hearing loss (SNHL) as par with the normal hearing listeners. The aim of this study was to evaluate the outcome of paediatric cochlear implantation in auditory and speech skills below the age of 5 years. The present study consisted of 50 childrens. Auditory skills were assessed in terms of audiometric thresholds and localization abilities. Speech - Language skills were measured using; Categories of Auditory Performance -CAP; Meaningful Use of Speech Scale - MUSS; Meaningful Auditory Integration Scale - MAIS and Speech intelligibility Rating - SIR. Hearing thresholds obtained from all the subjects for pre implant and post implant conditions of 3rd, 6th, 9th, 12th month conditions, evidenced a high significant (p < 0.001) improvement across all test frequencies 500, 1000, 2000 and 4000 Hz. There was also a statistically significant difference across successive measurements of auditory and speech skills, as determined by ANOVA (F (4, 245) = 151.33, p < 0.001 for CAP; F (4, 245) = 89.636, p < 0.001 for SIR; F (4, 245) = 812.282 p < 0.001 for MAIS and F(4, 245) = 435.677 p < 0.001 for MUSS). Auditory localization abilities were also improved considerably over a period of one year. The present study added the evidence to the literature that cochlear implants significantly improved the hearing ability of children with severe-to-profound hearing loss. This study also demonstrated that, children were better able to make use of the auditory information perceived through the implant.

Two cases of non-parasitic splenic cysts and spleen-preserving therapy.

We review two different presentations of non-parasitic splenic cysts, both of which are post-traumatic in aetiology. The first case was of slower onset and was managed electively. The second case was of acute onset and was managed as an emergency. Non-parasitic splenic cysts are uncommon and the optimal management strategy for them is not well defined. Historically, treatment has been with open splenectomy; however, infection rates following this surgery have been high, making it an unattractive management option. Both cases were managed successfully with laparoscopic fenestration with no recurrence at subsequent follow-up.

Acoustic Reflexes in Individuals Having Hyperacusis of the Auditory Origin.

Functional role of the acoustic reflex in preventing over stimulation of the inner auditory system by decreasing sound intensity along with the previous reports of acoustic reflex abnormalities in individuals having hyperacusis point towards the involvement of acoustic reflex deficit in the origin of hyperacusis especially when any medical condition leading to hyperacusis is not associated. However this issue remains contradictory owing to limited comprehensive investigation. This study was undertaken to ascertain the relationship between hyperacusis and the acoustic reflex. Threshold, amplitude and latency of the acoustic reflex were measured in two different groups of individuals having hyperacusis; Group 1: 14 individuals having hyperacusis with hearing loss (HwHL) and Group 2: 17 individuals having hyperacusis without hearing loss (HwoHL). Control group (Group 3) consisted of 15 normal hearing individuals who never experienced hyperacusis. Result showed a significant group effect on all the measured characteristics of the acoustic reflex. ARTs were found to be significantly higher in HwHL and HwoHL when compared to NHwoH. ARTs were statistically similar for HwoHL and NHwoH. HwoHL's ARAs and ARLs were significantly smaller and prolonged, respectively, when compared to HwHL and NHwoH. HwHL and NHwoH had statistically similar ARAs and ARLs. This study confirms acoustic reflex abnormalities in some individuals having hyperacusis with or without hearing loss. It further highlight the importance of involving acoustic reflex testing in the assessment of hyperacusis especially when hyperacusis is not associated with hearing loss or any other medical condition that may lead to hyperacusis.

Efficacy of Itraconazole in the Prevention of Recurrence of Tinea Versicolor: A Three Year Follow Up.

Pityriasis versicolor (PV) also known as tinea versicolor, which is chronic and superficial fungal skin disease caused by Malassezia yeasts. A permanent cure may difficult to achieve and this may explain the long-term nature of the disease. Consequently, a preventive treatment regimen may help to prevent the recurrence of pityriasis versicolor. Whether, the recurrence of tinea versicolor could be prevented by monthly itraconazole treatment regimen after a short course of itraconazole therapy. Open treatment followed by a randomized, single blind placebo control trial. Multi-center trial was characterized by an open, active treatment phase with itraconazole followed by a randomized placebo controlled treatment for prevention of recurrence. A total 200 patients (150 male and 50 female) were included in this study and was given 200mg itraconazole daily for 7 days (treatment phase). Patients in whom tinea versicolor was mycologically cured divided into Group A and Group B. Active open treatment was followed by preventive itraconazole treatment 200mg twice daily in Group A and placebo in Group B monthly for 6 consecutive months. The patients were diagnosed clinically and confirmed by Wood's lamp examination and KOH microscopy. Clinical improvement in 90%, negative Wood's lamp examination in 86.5% and Mycological cure in 85.5% were found at the end of open treatment. The mycological cure, 171 subjects were taken into this study for preventive treatment phase and divided into two groups- Group A & Group B. Preventive treatment was given in Group A and placebo in Group B. After the preventive treatment, the end point (After 6 months), clinical improvement, negative Wood's lamp examination and mycological cure were found in 81(90%), 76(84.4%) and 75(83.3%) in Group A and 44(55%), 41(51.3%) and 42(52.5%) in Group B respectively. In preventive treatment phase, 1 patient in Group A did not complete the study. No patient experienced any serious adverse effects. Prevention of recurrence of Pityriasis versicolor with itraconazole is as effective as treatment.

Successful Management of Phaeochromocytoma using Preoperative Oral Labetalol and Intraoperative Magnesium Sulphate: Report of four cases.

Phaeochromocytoma is a rare neuroendocrine catecholamine-secreting tumour. This type of tumour poses multidimensional anaesthetic challenges as it has an unpredictable clinical course during surgical resection. The alpha-blocking agent phenoxybenzamine remained the mainstay in preoperative preparation before the introduction of beta-blocking agents. We report four cases operated between 2009-2012 at Sultan Qaboos University Hospital, Muscat, Oman. The cases were prepared with oral labetalol, as the alpha-blocking drug phenoxybenzamine was not immediately available. Responses to simulated stress were tested in the theatre before surgery. Anaesthesia was induced under invasive arterial pressure monitoring and magnesium sulphate infusion. Rare intraoperative surges in blood pressure during tumour manipulation were treated with sodium nitroprusside infusions and phentolamine boluses. All of the patients had an uneventful postoperative recovery. Preoperative treatment with labetalol has rarely been reported and can be considered as a potential therapeutic option with optimal patient monitoring if phenoxybenzamine is unavailable.

The role of auditory and kinaesthetic feedback mechanisms on phonatory stability in children.

Auditory feedback plays an important role in phonatory control. When auditory feedback is disrupted, various changes are observed in vocal motor control. Vocal intensity and fundamental frequency (F0) levels tend to increase in response to auditory masking. Because of the close reflexive links between the auditory and phonatory systems, it is likely that phonatory stability may be disrupted when auditory feedback is disrupted or altered. However, studies on phonatory stability under auditory masking condition in adult subjects showed that most of the subjects maintained normal levels of phonatory stability. The authors in the earlier investigations suggested that auditory feedback is not the sole contributor to vocal motor control and phonatory stability, a complex neuromuscular reflex system known as kinaesthetic feedback may play a role in controlling phonatory stability when auditory feedback is disrupted or lacking. This proposes the need to further investigate this phenomenon as to whether children show similar patterns of phonatory stability under auditory masking since their neuromotor systems are still at developmental stage, less mature and are less resistant to altered auditory feedback than adults. A total of 40 normal hearing and speaking children (20 male and 20 female) between the age group of 6 and 8 years participated as subjects. The acoustic parameters such as shimmer, jitter and harmonic-to-noise ratio (HNR) were measures and compared between no masking condition (0 dB ML) and masking condition (90 dB ML). Despite the neuromotor systems being less mature in children and less resistant than adults to altered auditory feedback, most of the children in the study demonstrated increased phonatory stability which was reflected by reduced shimmer, jitter and increased HNR values. This study implicates that most of the children demonstrate well established patterns of kinaesthetic feedback, which might have allowed them to maintain normal levels of vocal motor control even in the presence of disturbed auditory feedback. Hence, it can be concluded that children also exhibit kinaesthetic feedback mechanism to control phonatory stability when auditory feedback is disrupted which in turn highlights the importance of kinaesthetic feedback to be included in the therapeutic/intervention approaches for children with hearing and neurogenic speech deficits.

Speech recognition performance in children with cochlear implants using bimodal stimulation.

Cochlear implantees have considerably good speech understanding abilities in quiet surroundings. But, ambient noise poses significant difficulties in understanding speech for these individuals. Bimodal stimulation is still not used by many Indian implantees in spite of reports that bimodal stimulation is beneficial for speech understanding in noise as compared to cochlear implant alone and also prevents auditory deprivation in the un-implanted ear. The aim of the study is to evaluate the benefits of bimodal stimulation in children in an Indian cochlear implant clinic. A group of 14 children who have been using cochlear implants served as subjects in this study. They were fitted with advanced digital hearing aids in their un-implanted ears to provide bimodal stimulation. Results revealed that bimodal stimulation did not bring greater change in speech scores in quiet surroundings but have shown a noticeable improvement in noisy ambience. Hence the present study suggests that bimodal stimulation would benefit children with cochlear implants especially in adverse listening conditions.

Assessment of groundwater corrosiveness for unconfined aquifer system at Kalpakkam.

Groundwater samples from the shallow unconfined aquifer were collected from fifteen borewells in Kalpakkam nuclear plant site and were analysed for various physico-chemical parameters. The pH, temperature, salinity, TDS and EC were measured in the field. The borewell samples were analysed in the laboratory for Ca(2+), Mg(2+), Na(+), Cl(-), CO(2-)(3), HC(O-)(3), N(O-)(3) and SO(2-)(4). The Piper Trilinear diagram showed that majority of the borewell samples fall in Na - Cl +SO(4) type and Na - CO(3)+HCO(3) type. The Cl: HCO3 ratio of some borewell samples are categorized under injuriously contaminated to highly injurious type. The higher salinity levels encountered in some borewells emphasized the need for better understanding of groundwater corrosiveness. Accordingly, the Langeliar saturation Index (SI), Aggressivity index (AI) and Larson ratio (LnR) were evaluated for assessing the corrosive nature of the groundwater. The saline water incursion in the southern part of the study area increased the ionic concentration of Cl(-) and [Formula: see text] that made the groundwater corrosive.

Tuberculosis in chronic kidney disease.

BACKGROUND: The incidence of tuberculosis is high in chronic kidney disease (CKD) which needs a high index of suspicion, early diagnosis and management for gratifying outcome. MATERIALS: The clinical, laboratory profile, management and outcome of tuberculosis in 36 patients with chronic kidney disease between 2000 and 2005 constitute the material of this study. RESULTS: During this study period, over 900 chronic renal failure patients were evaluated in our unit and 36 of them were found to have tuberculosis, the incidence being 4%. In majority (69.4%), tuberculosis was observed in association with CKD Stage V. Age range was 25 - 77 years, male : female ratio was 33 : 3. Fever, malaise and weight loss were the commonest symptoms observed at presentation. Extrapulmonary tuberculosis (23 patients, 63.8%) predominated over pulmonary tuberculosis (10 patients, 36.1%). Tuberculin skin test was negative in 23 patients (63.8%). The diagnosis of tuberculosis was confirmed by tissue or specimen examination in 17 patients (47.2%) and in the rest it was empirical basing on clinical picture, pleural fluid analysis and radiological tests. All the patients were planned for a minimum period of 9-month antituberculous therapy (ATT). Of them, 17 patients (47.2%) were cured from tuberculosis and did not relapse, 9 patients (25%) died during treatment and 10 patients were lost for follow-up. Two patients were managed for anti-tuberculous therapy-related side effects: hepatotoxicity and psychosis. CONCLUSIONS: We observed a 4% incidence of tuberculosis in CKD. Extrapulmonary form of tuberculosis predominated over pulmonary form. Fever and malaise were important clues for suspicion of tuberculosis. Tuberculin skin test was negative in the majority. Diagnostic confirmation was possible in 47.2% of patients and in the rest it was based on clinical suspicion, pleural fluid analysis and radiological findings. Cure from tuberculosis was observed in 47.2% of patients with antituberculous therapy.

Dielectric properties of certain biological materials at microwave frequencies.

In the medical field, microwaves play a larger role for treatment than diagnosis. For the detection of diseases by microwave methods, it is essential to know the dielectric properties of biological materials. For the present study, a cavity perturbation technique was employed to determine the dielectric properties of these materials. Rectangular cavity resonators were used to measure the complex permittivity of human bile, bile stones, gastric juice and saliva. The measurements were carried out in the S and J bands. It is observed that normal and infected bile have different dielectric constant and loss tangent. Dielectric constant of infected bile and gastric juice varies from patient to patient. Detection and extraction of bile stone with possible method of treatment is also discussed.

Neurotrophic actions of a novel molluscan epidermal growth factor.

The mammalian epidermal growth factor (EGF) is expressed in the developing and adult CNS, and it has been implicated in the control of cell proliferation, differentiation, and neurotrophic events. Despite extensive evolutionary conservation of the EGF motif in a range of different types of proteins, secreted EGF homologs with neurotrophic actions have not been reported in invertebrates. In this study, we present a novel member of the family of EGF-like growth factors, an EGF homolog from the mollusc Lymnaea stagnalis (L-EGF), and we demonstrate that this protein has neurotrophic activity. Purified L-EGF is a 43-residue peptide and retains the typical structural characteristics of the EGF motif. The L-EGF cDNA reveals a unique precursor organization. In contrast to the multidomain mammalian EGFs, it consists of only two domains, a signal peptide and a single EGF motif. Conspicuously, the L-EGF precursor lacks a transmembrane domain, setting it apart from all other members of the EGF-family. L-EGF mRNA is expressed throughout embryonic development, in the juvenile CNS, but not in the normal adult CNS. However, expression in the adult CNS is upregulated after injury, suggesting a role of L-EGF in repair functions. This notion is supported by the observation that L-EGF evokes neurite outgrowth in specific adult Lymnaea neurons in vitro, which could be inhibited by an EGF receptor tyrosine kinase inhibitor. In conclusion, our findings further substantiate the notion that the EGF family has an early phylogenetic origin, and our data support a neurotrophic role for L-EGF during development and injury repair.

Primary structure of a new neuropeptide, cerebral peptide 2, purified from cerebral ganglia of Aplysia.

We report the purification and characterization of a novel neuropeptide from Aplysia nervous tissue. The peptide was termed cerebral peptide 2 (CP2) because it was the larger of two peptides predominantly synthesized in the cerebral ganglia and transported to other regions of the central nervous system. The purification of CP2 from extracts of cerebral ganglia using three sequential modes of high-pressure liquid chromatography (HPLC) was followed using the [35S]methionine-labeled peptide obtained from transport experiments. The primary structure of CP2 was determined by automated Edman degradation of native CP2 and its proteolytic fragments in conjunction with mass spectrometry. CP2 is a 41 amino acid peptide with an amidated carboxyl terminal. A peptide with the proposed sequence of CP2 was synthetized and compared by HPLC with the native peptide. Chromatographic properties of the synthetic and native peptide labeled in vivo were found to be identical. CP2 does not appear to be a member of any previously identified peptide family.

Molecular mimicry: histone H3 and mycobacterial protein epitopes.

A 15-kDa protein detected initially in amyloidotic ileum from a transgenic mouse and subsequently in control (nontransgenic) ileum by various polyclonal rabbit antiserums applied to electroblots of extracts derived from these tissues was identified by partial sequence analysis as histone H3. Antiserums were made against immunogens unrelated to the histone, but they recognized calf thymus histone H3 (14.7 kDa) on Western blots. The bacterial component of the Freund's medium used as an adjuvant for the immunogens was either Mycobacterium butyricum or Mycobacterium smegmatis. Absorption tests with histone H3 and sonicated M. butyricum substantiated the presence of anti-histone H3 activity in the antiserums. These findings indicate that the two mycobacterium species make a protein with epitopes perceived as nonself by recipient rabbits but sufficiently similar to epitopes of mammalian histone H3 that the rabbits produced antibodies cross-reactive with the histone.

Platelet-derived growth factor-BB accelerates wound closure in a new mesentery culture model without macrophages.

Platelet-derived growth factor-BB has multiple effects in vitro and has been demonstrated to accelerate wound healing in several animal models, but its precise mechanisms of action in vivo have not been fully explained. A rat mesentery culture model was developed, and platelet-derived growth factor-BB (100 ng/ml) was added to the medium containing 2% fetal calf serum for examining its closure effects. The mesentery specimens were stained by routine hematoxylin and eosin and immunohistochemical staining for macrophages. A significant improvement in closure rate and complete closure rate was seen when platelet-derived growth factor-BB was added to the medium compared with the controls (p < 0.05). There are significantly fewer macrophages in the in vitro specimen than in the in vivo specimen. In conclusion, platelet-derived growth factor-BB can contribute to wound closure of a mesenteric defect even without macrophages, suggesting a second mechanism in which it can act directly on mesenchymal cells during wound healing. This tissue-culture model is useful for gaining further insights into growth factor interactions and wound healing.