Personal concept of chronic illness in rural population-identifying myths and beliefs

Background: The morbidity of Chronic Renal Failure (CRF) is not only physical but also psychological and social. The study aimed at identifying whether there was any mythological belief in being afflicted with such a chronic illness and the personal concept of a chronic illness. Therefore patients with chronic renal failure were selected for the study.  Methods: The study includes two different groups of patients, 25 per group examined at two different places at two different points of time. The two groups attended different hospitals in their local areas. Patients who were suffering from chronic renal failure were examined and selected for the study. In both groups results were obtained based on questions designed to get information on four themes: their economic status, their status of work, their dependency status and their personal concept of the illness. All the patients belong to rural areas and have had less than formal education or no education at all.Results: The most important finding in this study was a belief expressed in five patients (Two males and three female). They believed that indulging in sex in their marital life itself was a cause of the illness. One other female patient who had a bad obstetric history felt that her illness was due to the number of abortions she had.Conclusion: In a country like India especially in rural India where people believe in alternative medicine, magico-religious methods of native healers, it is difficult to convince people to go for a counselling service. They have to be provided such a service after the initial physical treatments have been started. It is essential that a service of such kind is provided free of cost at any level, even in a primary health centre. Where possible it is necessary to use diagnostic tools to designate severity of the problem. Otherwise personal ideas about illness that marital life has caused the disease can reflect adversely on the harmony and quality of life of patients. This study has enough potential to conduct more such studies to identify outcomes of chronic illnesses and design interventions accordingly.

Sequential decision fusion for controlled detection errors

Information fusion in biometrics has received considerable attention. The architecture proposed here is based on the sequential integration of multi-instance and multi-sample fusion schemes. This method is analytically shown to improve the performance and allow a controlled trade-off between false alarms and false rejects when the classifier decisions are statistically independent. Equations developed for detection error rates are experimentally evaluated by considering the proposed architecture for text dependent speaker verification using HMM based digit dependent speaker models. The tuning of parameters, n classifiers and m attempts/samples, is investigated and the resultant detection error trade-off performance is evaluated on individual digits. Results show that performance improvement can be achieved even for weaker classifiers (FRR-19.6%, FAR-16.7%). The architectures investigated apply to speaker verification from spoken digit strings such as credit card numbers in telephone or VOIP or internet based applications

Communicating root of auriculotemporal nerve with inferior alveolar nerve-looping around accessory meningeal artery

Background: The auriculotemporal nerve has been described as having two roots in standard textbooks of anatomy. It lies on the tensor veli palatini muscle while passing backwards behind the lateral pterygoid muscle. It runs behind the temporomandibular joint after passing between the sphenomandibular ligament and the neck of mandible. It ascends over the posterior root of zygoma posterior to superficial temporal vessels. It gives superficial temporal branches and also branches to facial nerve and otic ganglion. The branches to the facial nerve join at the posterior border of masseter. On the face the cutaneous branches supply the tragus, part of the adjoining auricle of the ear and posterior part of temple.Methods: Variations in the origin of the auriculotemporal nerve have been described by many authors in the past and this prompted the study of the auriculotemporal nerve, its origin and course, in 36 specimens (18 cadaveric heads) in bodies that were allotted for dissection purpose to first year medical students in the department of anatomy in P.E.S Medical College, Kuppam.Results: It was seen that the auriculotemporal nerve had two roots of origin and they formed a loop to enclose the middle meningeal artery in all the 35 specimens except in one side of the cadaveric heads. In only one half of a cadaveric head it was found to arise by three roots which formed two nerve loops. The first and second nerve roots joined with each other to form a nerve loop. The third root joined with the inferior alveolar nerve and formed the second nerve loop. The accessory meningeal artery passed through the second nerve loop. The normal presentation of two roots enclosing the middle meningeal artery was not present. Instead the accessory meningeal artery was enclosed between the third root and the inferior alveolar nerve. The middle meningeal artery entered the skull through the foramen spinosum as usual but was not enclosed by the nerve roots. The trunk of the auriculo temporal nerve was seen between the middle meningeal artery and inferior alveolar nerve and the study reports the presence of variant nerve loops encircling the accessory meningeal artery.  Conclusion: The variations in the roots of auriculotemporal nerve have been reported in the past and since it is important in the clinical implications of the region especially for the facio-maxillary surgeons and dental surgeons. The incidence of variation has to be documented as this helps in updating the clinical database for surgical procedures and treatment in the region of infratemporal fossa.

Histo-pathological findings in kidneys with polar artery: a demystifying endeavor

Background: The kidneys are supplied by renal arteries which enter the hilum and branch progressively from the pyramids to the cortex into lobar, interlobar, arcuate, interlobar, interlobular, and finally terminate as afferent arterioles that enter the glomeruli. Thus there is a normal pattern of blood flow towards the cortex from the pyramids when the artery enters at the hilum. The aim of the study was to explore the glomeruli pattern in kidneys with polar arteries.Methods: The study was conducted in the department of anatomy at a tertiary care referral institute. Twenty-two kidneys with polar arteries were obtained by conventional method of dissection from cadavers for the study. Sections were taken from the upper pole and lower pole in each kidney. The sections were taken perpendicular and close to the polar arteries. The sections were subjected to routine histological processing and staining as per the standard operating procedure. Histological findings were observed and documented.Results: The study found that the kidneys were histologically different with polar arteries as compared to normal kidneys. The number of glomeruli per high power field was higher nearer to the polar arteries. The glomeruli were viable and not sclerosed. An agglomeration of arterioles were present close to the polar arteries but they were distinct and did not seem to be associated with glomeruli.    Conclusions: The study found an agglomeration of arterioles, increased number of viable glomeruli and cystic changes associated with kidneys having polar artery. Thus this warrants a detailed study with special stains for research to elucidate the mechanisms of the circulation in polar arteries and correlation of the same findings with clinical conditions such as hypertension or any other diseases of the kidney

SPECTRAL EFFICIENCY MAXIMIZATION IN MISO-OFDM SYSTEMS USING RATE ADAPTIVE BIT LOADING AND TRANSMIT ANTENNA SELECTION TECHNIQUES

A high spectral efficient system is expected to meet the growing demands of multimedia applications through a wireless medium. In this paper, a low complex high spectral efficient Reduced Multiple Input Single Output (R-MISO)-Orthogonal Frequency Division Multiplexing (OFDM) system is proposed. The proposed system exploits the benefits of Rate Adaptive Bit Loading (RABL), Transmit Antenna Selection (TAS) and Space Frequency Block Codes (SFBC) to get high spectral efficiency through a constrained available spectrum. The performance of the proposed system with different configurations of R-MISO is analyzed with the average Signal to Noise Ratio (SNR) gain, Bit Error Rate (BER), outage probability, spectral efficiency and data rate. The performance of the proposed system has greatly enhanced by utilizing TAS and RABL techniques. The obtained simulation results validate this statement

Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation

Previous studies have shown that the translation level of in vitro transcribed messenger RNA (mRNA) is enhanced when its uridines are replaced with pseudouridines; however, the reason for this enhancement has not been identified. Here, we demonstrate that in vitro transcripts containing uridine activate RNA-dependent protein kinase (PKR), which then phosphorylates translation initiation factor 2-alpha (eIF-2α), and inhibits translation. In contrast, in vitro transcribed mRNAs containing pseudouridine activate PKR to a lesser degree, and translation of pseudouridine-containing mRNAs is not repressed. RNA pull-down assays demonstrate that mRNA containing uridine is bound by PKR more efficiently than mRNA with pseudouridine. Finally, the role of PKR is validated by showing that pseudouridine- and uridine-containing RNAs were translated equally in PKR knockout cells. These results indicate that the enhanced translation of mRNAs containing pseudouridine, compared to those containing uridine, is mediated by decreased activation of PKR

Increased Erythropoiesis in Mice Injected With Submicrogram Quantities of Pseudouridine-containing mRNA Encoding Erythropoietin

Advances in the optimization of in vitro-transcribed mRNA are bringing mRNA-mediated therapy closer to reality. In cultured cells, we recently achieved high levels of translation with high-performance liquid chromatography (HPLC)-purified, in vitro-transcribed mRNAs containing the modified nucleoside pseudouridine. Importantly, pseudouridine rendered the mRNA non-immunogenic. Here, using erythropoietin (EPO)-encoding mRNA complexed with TransIT-mRNA, we evaluated this new generation of mRNA in vivo. A single injection of 100 ng (0.005 mg/kg) mRNA elevated serum EPO levels in mice significantly by 6 hours and levels were maintained for 4 days. In comparison, mRNA containing uridine produced 10–100-fold lower levels of EPO lasting only 1 day. EPO translated from pseudouridine-mRNA was functional and caused a significant increase of both reticulocyte counts and hematocrits. As little as 10 ng mRNA doubled reticulocyte numbers. Weekly injection of 100 ng of EPO mRNA was sufficient to increase the hematocrit from 43 to 57%, which was maintained with continued treatment. Even when a large amount of pseudouridine-mRNA was injected, no inflammatory cytokines were detectable in plasma. Using macaques, we could also detect significantly-increased serum EPO levels following intraperitoneal injection of rhesus EPO mRNA. These results demonstrate that HPLC-purified, pseudouridine-containing mRNAs encoding therapeutic proteins have great potential for clinical applications

Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5

The 5'-cap-structures of higher eukaryote mRNAs are ribose 2'-O-methylated. Likewise, a number of viruses replicating in the cytoplasm of eukayotes have evolved 2'-O-methyltransferases to modify autonomously their mRNAs. However, a defined biological role of mRNA 2'-O-methylation remains elusive. Here we show that viral mRNA 2'-O-methylation is critically involved in subversion of type-I-interferon (IFN-I) induction. We demonstrate that human and murine coronavirus 2'-O-methyltransferase mutants induce increased IFN-I expression, and are highly IFN-I sensitive. Importantly, IFN-I induction by 2'-O-methyltransferase-deficient viruses is dependent on the cytoplasmic RNA sensor melanoma differentiation-associated gene 5 (MDA5). This link between MDA5-mediated sensing of viral RNA and mRNA 2'-O-methylation suggests that RNA modifications, such as 2'-O-methylation, provide a molecular signature for the discrimination of self and non-self mRNA

Native Tertiary Structure and Nucleoside Modifications Suppress tRNA's Intrinsic Ability to Activate the Innate Immune Sensor PKR

Interferon inducible protein kinase PKR is an essential component of innate immunity. It is activated by long stretches of dsRNA and provides the first line of host defense against pathogens by inhibiting translation initiation in the infected cell. Many cellular and viral transcripts contain nucleoside modifications and/or tertiary structure that could affect PKR activation. We have previously demonstrated that a 5′-end triphosphate-a signature of certain viral and bacterial transcripts-confers the ability of relatively unstructured model RNA transcripts to activate PKR to inhibit translation, and that this activation is abrogated by certain modifications present in cellular RNAs. In order to understand the biological implications of native RNA tertiary structure and nucleoside modifications on PKR activation, we study here the heavily modified cellular tRNAs and the unmodified or the lightly modified mitochondrial tRNAs (mt-tRNA). We find that both a T7 transcript of yeast tRNAPhe and natively extracted total bovine liver mt-tRNA activate PKR in vitro, whereas native E. coli, bovine liver, yeast, and wheat tRNAPhe do not, nor do a variety of base- or sugar-modified T7 transcripts. These results are further supported by activation of PKR by a natively folded T7 transcript of tRNAPhe in vivo supporting the importance of tRNA modification in suppressing PKR activation in cells. We also examine PKR activation by a T7 transcript of the A14G pathogenic mutant of mt-tRNALeu, which is known to dimerize, and find that the misfolded dimeric form activates PKR in vitro while the monomeric form does not. Overall, the in vitro and in vivo findings herein indicate that tRNAs have an intrinsic ability to activate PKR and that nucleoside modifications and native RNA tertiary folding may function, at least in part, to suppress such activation, thus serving to distinguish self and non-self tRNA in innate immunity

Evading innate immunity in nonviral mRNA delivery : don't shoot the messenger

In de field of non-viral gene therapy, in vitro transcribed (IVT) mRNA has emerged as a promising tool for the delivery of genetic information. Over the past few years it has become widely known the introduction of IVT mRNA into mammalian cells elicits an innate immune response which has favored mRNA use towards immunotherapeutic vaccination strategies. However, for non-immunotherapy related applications this intrinsic immune-stimulatory activity directly interferes with the aimed therapeutic outcome, as it can seriously compromise the expression of the desired protein. This review presents an overview of the immune-related obstacles that limit mRNA advance for non-immunotherapy related applications