Novel Biomarkers of Health and Degeneration in Human Intervertebral Discs: In-depth Proteomic Analysis of Collagen Framework of Fetal, Healthy, Scoliotic, Degenerate, and Herniated Discs

Methods@#Forty NP tissues were snap-frozen in liquid nitrogen (–196°C) immediately before being subjected to proteomic and bioinformatic analyses from five different disk phenotypes (eight each). @*Results@#Tandem mass spectrometric analysis revealed a total of 1,050 proteins in FDs, 1,809 in ND, 1,487 in SD, 1,859 in DH, and 1,538 in the DD group. Of 28 major collagens reported in the human body, this study identified 24 different collagens with 34 subtypes in NP. Fibril-forming collagens (COL-1, 2, and 11A1) and fibril-associated collagens with interrupted triple helices (COL-9A1, 12A1, and 14A1) were abundantly expressed in FDs, representing their role in the development of NP. Multiplexin (COL-15), a hybrid proteoglycan–collagen molecule, was discovered only in FDs. Degeneration was associated with COL2A1 downregulation and COL-10A1 upregulation. @*Conclusions@#COL10 was discovered to be a new biomarker for disk degeneration. Besides COL-1 and 2, other important COLs (6, 9, 11, 12, 14, 15) with anabolic potential and abundant expression in the fetal phenotype could be investigated for tissue engineering and novel DDD therapy.

In Vertebral Hemangiomas with Neurological Deficit, Is a Less Extensive Approach Adequate

Methods@#Twenty-one patients who underwent surgery for AVH between 2009 and 2018 were analyzed. Demographic and clinical details of patients were retrieved from hospital information system. Imaging information (i.e., radiography, computed tomography, magnetic resonance imaging) of all patients was accessed and analyzed in picture archiving and communication system. Tumor staging was performed using Enneking and Weinstein–Boriani–Biagini classifications and Spinal Instability Neoplastic Score. At followup, neurological and radiological evaluations were performed. @*Results@#Twenty-one patients (13 [61.9%] females and 8 [38.1%] males) were included with a mean age of 44.29 years (range, 14–72 years). All patients in the study had neurological deficit. Back pain was present in 80.9% of patients. Mean duration of symptoms was 4.6 months (range, 1 day to 10 months). Most common lesion location was thoracic spine (n=12), followed by thoracolumbar (D11– L2; n=7) and lumbar (n=2) regions. Ten patients had multiple level lesions. All patients underwent preoperative embolization. Nine patients underwent intralesional spondylectomy with reconstruction; another nine patients underwent stabilization, decompression, and vertebroplasty; three patients underwent decompression and stabilization. Neurology improved in all patients, and only one case of recurrence was noted in a mean follow-up of 55.78±25 months (range, 24–96 months). @*Conclusions@#In AVH, good clinical and neurological outcomes with low recurrence rates can be achieved using less extensive procedures, such as posterior instrumented decompression with vertebroplasty and intralesional tumor resection.

Definitive Radiotherapy versus Surgery for the Treatment of Verrucous Carcinoma of the Larynx: A National Cancer Database Study

Abstract Introduction Traditionally, larger lesions of laryngeal verrucous carcinoma are treated with surgical excision, with definitive radiotherapy generally reserved for smaller lesions. However, data utilizing modern databases is limited. Objective The authors sought to assess, utilizing the National Cancer Database, whether overall survival for patients with laryngeal verrucous carcinoma was equivalent when treated with definitive radiotherapy versus definitive surgery. Methods A retrospective cohort study was conducted utilizing the National Cancer Database. All cases of laryngeal verrucous carcinoma within the National Cancer Database between 2006 and 2014 were reviewed. Patients with T1-T3 (American Joint Commission on Cancer 7th Edition) laryngeal verrucous carcinoma were included and stratified by treatment modality. Demographics, treatment, and survival data were analyzed. Results A total of 392 patients were included. Two hundred and fifty patients underwent surgery and 142 received radiotherapy. The two groups differed in age, transition of care, clinical T stage, and clinical stages. There was no significant difference in survival between T1-T3 lesions treated with surgery or radiotherapy (p =0.32). Age, comorbidities, insurance status, and clinical T stage impacted overall hazard on multivariate analysis (p <0.01). For patients treated with radiotherapy, age, insurance status, and clinical T stage were predictive of increased hazard. Conclusion Overall survival is equivalent for patients with clinical T1 and clinical T2 laryngeal verrucous carcinoma treated with primary radiotherapy versus primary surgery. Thus, radiotherapy should be considered as a non-inferior treatment modality for certain patients with laryngeal verrucous carcinoma.

Indian Diabetes Risk Score (IDRS): An effective tool to screen undiagnosed diabetes

Background: Diabetes is an insidious public health problem. India has the second largest number of adults living with diabetes worldwide (77 million). Indian Diabetes Risk Score (IDRS) is a simple, cost-effective and feasible tool for mass screening programme at community level. Aim & Objective: To assess diabetes risk in adults aged 30 years and above and to identify high risk subjects for screening undiagnosed diabetes in an urban population of Meerut. Settings and Design: Community based cross-sectional study. Methods and Material: All adults who were ?30 years of age and non-diabetic were interviewed using pre-designed, pre-tested questionnaire for their socio-demographic profile and lifestyle. Fasting Blood glucose of all study subjects were done to screen undiagnosed diabetics. Statistical analysis used: Centers for Disease Control (CDC), Epi Info TM 7.2.3.1 was used. Pearson’s Chi Square were applied. Results: 33.4% were found to have high diabetes risk. Risk of diabetes increases with age. 7.6% of the study subjects were found to be diabetic and were unaware of their diabetic status. Physical inactivity and increasing waist circumference were found to be significantly associated with risk of diabetes. Diabetes risk was also significantly associated with positive family history. Conclusions: Screening and early identification of high risk individuals would help in early diagnosis and treatment to prevent or to delay the onset of diabetes mellitus and its complications.

In-Silico Analysis of Chromatin Modifiers and Profiling of Histone Deacetylases (HDAC’s) in Human Oral Cancer / 전남의대학술지

Histone modifications have been demonstrated to play a significant role in oral squamous cell carcinoma (OSCC) epigenetic regulation. An in-silico analysis of The Cancer Genome Atlas (TCGA) of various histone acetyl transferases (HATs) and histone deacetylases (HDACs) suggested that HATs do not differ between normal and tumor samples whereas HDAC2 and HDAC1 change maximally and marginally respectively between normal and tumor patients with no change being noted in HDAC6 expression. Hence, this investigation was carried out to validate the expression states of HDAC 1, 2 and 6 mRNAs in buccal mucosa and tongue SCC samples in an Indian cohort. Buccal mucosa and tongue squamous cell carcinoma tissues with intact histopathology were processed for RNA isolation followed by cDNA synthesis which was then subjected to q-PCR for HDACs. The average RNA yield of the tongue tissue sample was ∼2 μg/mg of tissue and the A260/280 ratios were between 2.03 and 2.06. The average RNA yield of buccal mucosa tissue sample was ∼1 μg/mg of tissue and the A260/280 ratio were between 2.00 and 2.08. We have demonstrated that HDAC2 was overexpressed in tongue and buccal mucosa samples. Over-expression of HDAC2 imply potential use of HDACi along with standard chemotherapeutic drug in oral cancer treatment.

Impact of Patient Counseling and Socioeconomic Factors on Initiation of Rehabilitation Program in Spinal Cord Injury Patients Presenting to a Tertiary Spine Unit in India

Study DesignProspective case series.PurposeThis study aimed to investigate the impact of education, financial income, occupation, and patient counseling on the timing of enrolment in a spinal cord injury (SCI) rehabilitation program.Overview of LiteratureA rehabilitation program following SCI is essential to improve functional outcomes. Socioeconomic factors can affect the timing of enrolment to a rehabilitation program. Literature on the effects of socioeconomic factors among patients with SCI in the Indian scenario is limited.MethodsA prospective, consecutive analysis of patients with SCI was performed with 1-year follow-up. Assessment of the timing of enrolment to a rehabilitation program was performed using the modified Kuppuswamy socioeconomic scores (MKSS). Patients admitted to the SCI unit (group A), underwent intensive individual, group, and family counseling sessions to encourage early enrolment into a rehabilitation program. Patients presenting directly for rehabilitation (group B) were analyzed for comparison.ResultsA total of 153 patients were recruited. Group A was composed of 122 patients who started the rehabilitation program after a mean of 28 days, compared with a mean of 149 days for 31 patients in group B. In group A, 104 patients (85%; mean MKSS, 14.02) and 18 patients (15%; mean MKSS, 15.61) enrolled for rehabilitation 0.05).Conclusions Early patient counseling in the acute care unit helps in the early enrolment of patients with poor socioeconomic demographic profile to a rehabilitation program.

In-Silico Analysis of Chromatin Modifiers and Profiling of Histone Deacetylases (HDAC’s) in Human Oral Cancer / 전남의대학술지

Histone modifications have been demonstrated to play a significant role in oral squamous cell carcinoma (OSCC) epigenetic regulation. An in-silico analysis of The Cancer Genome Atlas (TCGA) of various histone acetyl transferases (HATs) and histone deacetylases (HDACs) suggested that HATs do not differ between normal and tumor samples whereas HDAC2 and HDAC1 change maximally and marginally respectively between normal and tumor patients with no change being noted in HDAC6 expression. Hence, this investigation was carried out to validate the expression states of HDAC 1, 2 and 6 mRNAs in buccal mucosa and tongue SCC samples in an Indian cohort. Buccal mucosa and tongue squamous cell carcinoma tissues with intact histopathology were processed for RNA isolation followed by cDNA synthesis which was then subjected to q-PCR for HDACs. The average RNA yield of the tongue tissue sample was ∼2 μg/mg of tissue and the A260/280 ratios were between 2.03 and 2.06. The average RNA yield of buccal mucosa tissue sample was ∼1 μg/mg of tissue and the A260/280 ratio were between 2.00 and 2.08. We have demonstrated that HDAC2 was overexpressed in tongue and buccal mucosa samples. Over-expression of HDAC2 imply potential use of HDACi along with standard chemotherapeutic drug in oral cancer treatment.

Impact of Patient Counseling and Socioeconomic Factors on Initiation of Rehabilitation Program in Spinal Cord Injury Patients Presenting to a Tertiary Spine Unit in India

Study DesignProspective case series.PurposeThis study aimed to investigate the impact of education, financial income, occupation, and patient counseling on the timing of enrolment in a spinal cord injury (SCI) rehabilitation program.Overview of LiteratureA rehabilitation program following SCI is essential to improve functional outcomes. Socioeconomic factors can affect the timing of enrolment to a rehabilitation program. Literature on the effects of socioeconomic factors among patients with SCI in the Indian scenario is limited.MethodsA prospective, consecutive analysis of patients with SCI was performed with 1-year follow-up. Assessment of the timing of enrolment to a rehabilitation program was performed using the modified Kuppuswamy socioeconomic scores (MKSS). Patients admitted to the SCI unit (group A), underwent intensive individual, group, and family counseling sessions to encourage early enrolment into a rehabilitation program. Patients presenting directly for rehabilitation (group B) were analyzed for comparison.ResultsA total of 153 patients were recruited. Group A was composed of 122 patients who started the rehabilitation program after a mean of 28 days, compared with a mean of 149 days for 31 patients in group B. In group A, 104 patients (85%; mean MKSS, 14.02) and 18 patients (15%; mean MKSS, 15.61) enrolled for rehabilitation 0.05).Conclusions Early patient counseling in the acute care unit helps in the early enrolment of patients with poor socioeconomic demographic profile to a rehabilitation program.

MRI based volumetric analysis of entorhinal cortex in elderly subjects with mild cognitive impairment and in subjects with normal cognition to see effects of aging on volume of ERC

Background: MCI is a transitional period between normal ageing and clinically probable early Alzheimer’s Dementia (AD). ERC volumes show early reduction in cases of MCI in comparison to the normal ageing subjects. Early cognitive impairment can be documented with ERC atrophy on MR volumetry. Aim of the study was to evaluate the volume of entorhinal cortex in patients of MCI and  to compared the volume with patients of normal cognition. Secondarily, we studied changes in the volume of entorhinal cortex with increasing ageMethods: In this study 30 patients of 60 years and above with MCI and 30 controls of normal cognition (age and sex matched) underwent brain examination on 3T MRI. Volume of entorhinal cortex was measured on 1 mm thick T1 coronal oblique MR scans by manually tracing the boundaries defined by two widely used methods i.e. Insausti et al and Goncharova et al.Results: Patients with MCI showed 17.2% decline in the entorhinal cortex volume compared to controls (p value = 0.001). Patients of older age showed significantly more ERC volume reduction, reaching up to 30.4% in comparison to younger subjects suggesting atrophy of ERC in normal aging and in MCI both, but more so in patients with cognitive impairment.Conclusions: ERC atrophy was found in MCI cases more than controls, increase atrophy trend was noted with increasing age. MR volumetry may play a role for documentation of ERC atrophy in cases of MCI.

A prospective study of complications in newly diagnosed type 2 diabetes mellitus patients of lower socioeconomic group with special reference to microvascular complication and metabolic syndrome

Background: All these metabolic derangements exist for many years in the asymptomatic phase of type 2 diabetes and they predispose to development of complications even before clinical diagnosis. Metabolic syndrome is considered to be a precursor of type 2 diabetes. Present study is primarily aimed to study the prevalence of micro vascular complications and metabolic syndrome in newly diagnosed type 2 diabetes mellitus patients of low socio-economic group.Methods: This is a cross sectional prospective study conducted in the dept. of general medicine Konaseema institute of medical science Amalapuram, Andhra Pradesh, India from November 2016 to October 2018. Based on exclusion and inclusion criteria 103 patients were enrolled for this study. Various parameters like age, sex, body mass index, waist circumference, lipid profile, systolic and diastolic blood pressure, neuropathy, nephropathy and retinopathy was measured.Results: The mean age of the patient was 48±10.0 years. Fasting and 2 hours OGTT was 174.6±46.8 mg/dl and 255.6±75.6 mg/dl. The mean of total cholesterol was 204.7±41.9 (mg/dl), Triglycerides was 218±83.4 (mg/dl) and HDL was 44±5.3 (mg/dl). Symptomatic neuropathy constituted 35.6% in 51-60 age group and 27.1% in 31-40 and 41-50 age groups. Objective neuropathy constituted highest (36.6%) in 51-60 age group. Retinopathy constituted highest (60%) in 51-60 age group and nephropathy constituted 26.3 % in 21-30 and 51-60 age groups.Conclusions: Prevalence of microvascular complications in newly diagnosed diabetics of low socioeconomic group were as follows: symptomatic neuropathy-57.3%, objective neuropathy-39.8%, retinopathy-4.9%, nephropathy-18.4%. These were similar to published studies from general population from the same geographical area.

Chronic persistent post-surgical pain following staging laparotomy for carcinoma of ovary and its relationship to signal transduction genes

BACKGROUND: The present study was undertaken to evaluate the incidence of chronic persistent post-surgical pain (CPPP) and the role of signal transduction genes in patients undergoing staging laparotomy for carcinoma ovary. METHODS: The present observational study was undertaken following institutional ethical committee approval and informed consent from all the participants. A total 21 patients of ASA grade I to III with age 20−70 years, scheduled for elective staging laparotomy for carcinoma ovary were included. Patients were excluded if had other causes of pain, cognitive dysfunction or chronic neurological disorders. Statistical analysis of pool data was done using SPSS version-17. For various scales like GPE, PDQ, NPSI, the visual analogue scale (VAS), global perceived effect (GPE), the pain DETECT questionnaire (PDQ), and neuropathic pain symptoms inventory (NPSI), one factor repaeted measure ANOVA applied with simple contrast with baseline as on post-operative day 1 (considered as reference and compared with subsequent time-interval), and the P values were adjusted according to "Bonferroni adjustments". In patients with CPPP, the Δct values of mRNA expressions of genes at the end of postoperative day 90 were compared with the baseline control values by one factor repeated ANOVA. P value < 0.005 significant. RESULTS: The present study demonstrates 38.1% (8 out of 21 patients) incidence of CPPP. The functional status and quality of life as were observed to be significantly diminished in all patients with chronic pain. An up-regulation in the mRNA expression of signal transduction and a positive correlation was noted between the mRNA expression of signal transduction genes and VAS score in all patients with CPPP at the end of postoperative day 90. CONCLUSIONS: The reported incidence of CPPP in patients with carcinoma ovary was 38.1%. An up-regulation and positive correlation between mRNA expression of signal transduction genes and VAS score depicts its potential role in the pathogenesis of CPPP.

Chronic persistent post-surgical pain following staging laparotomy for carcinoma of ovary and its relationship to signal transduction genes

BACKGROUND: The present study was undertaken to evaluate the incidence of chronic persistent post-surgical pain (CPPP) and the role of signal transduction genes in patients undergoing staging laparotomy for carcinoma ovary. METHODS: The present observational study was undertaken following institutional ethical committee approval and informed consent from all the participants. A total 21 patients of ASA grade I to III with age 20−70 years, scheduled for elective staging laparotomy for carcinoma ovary were included. Patients were excluded if had other causes of pain, cognitive dysfunction or chronic neurological disorders. Statistical analysis of pool data was done using SPSS version-17. For various scales like GPE, PDQ, NPSI, the visual analogue scale (VAS), global perceived effect (GPE), the pain DETECT questionnaire (PDQ), and neuropathic pain symptoms inventory (NPSI), one factor repaeted measure ANOVA applied with simple contrast with baseline as on post-operative day 1 (considered as reference and compared with subsequent time-interval), and the P values were adjusted according to "Bonferroni adjustments". In patients with CPPP, the Δct values of mRNA expressions of genes at the end of postoperative day 90 were compared with the baseline control values by one factor repeated ANOVA. P value < 0.005 significant. RESULTS: The present study demonstrates 38.1% (8 out of 21 patients) incidence of CPPP. The functional status and quality of life as were observed to be significantly diminished in all patients with chronic pain. An up-regulation in the mRNA expression of signal transduction and a positive correlation was noted between the mRNA expression of signal transduction genes and VAS score in all patients with CPPP at the end of postoperative day 90. CONCLUSIONS: The reported incidence of CPPP in patients with carcinoma ovary was 38.1%. An up-regulation and positive correlation between mRNA expression of signal transduction genes and VAS score depicts its potential role in the pathogenesis of CPPP.

Congenital Juvenile Xanthogranuloma of Foot, a Nodular Lesion: An Unusual Case in 2-month-old Infant.

A 2-month-old infant presented with a circumscribed nodule on left foot since birth. Excision biopsy showed juvenile xanthogranuloma, an uncommon diagnosis in an unusual site; common sites being head and neck. Uncommon sites are groin, genital organs, limbs and even internal organs. It carries a favorable prognosis.

Combined pleural fluid cholesterol and total protein in differentiation of exudates and transudates.

Background. The management strategy to be adopted in pleural effusion depends on whether an effusion is a transudate or exudate. Objective. To evaluate the usefulness of pleural fluid cholesterol and/or total protein measurements for differentiating between exudates and transudates, and to compare it with Light’s criteria. Methods. In this prospective study 60 patients with pleural effusion were included. Pleural fluid total protein, lactate dehydrogenase (LDH) and cholesterol as well as serum total protein and LDH levels along with other investigations were studied. Clinical classification of transudate or exudate was done on the basis of aetiology. Results. Based on clinical signs and symptoms, chest radiograph, other investigations and response to treatment, 49 of these effusions were classified as exudates and 11 as transudates. Using pleural fluid cholesterol levels at a cut-off point of greater than 60 mg/dL and/or total protein at a cut-off point of greater than 3 g/dL for distinguishing transudates and exudates, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), were 100 percent. Using Light’s criteria for discriminating transudates and exudates, sensitivity, specificity, PPV and NPV were found to be 98%; 100%; 100% and 92%, respectively. The differences resulted from a mis-classification of one expected exudate as transudate by Light’s criteria. Conclusion. Pleural fluid cholesterol and total protein are simple, cost-effective, and useful parameters in distinguishing pleural transudates from exudates, with the advantage of requiring only two laboratory determinations and no simultaneous blood sample, compared to the use of Light’s criteria.

The hnRNP A1 homolog Hrp36 is essential for normal development, female fecundity, omega speckle formation and stress tolerance in Drosophila melanogaster.

Hrp36/Hrb87F is one of the most abundant and well-characterized hnRNP A homolog in Drosophila and is shown to have roles in regulation of alternative splicing, heterochromatin formation, neurodegeneration, etc. Yet, hrp36 null individuals were reported to be viable and without any apparent phenotype, presumably because of overlapping functions provided by Hrp38 and related proteins. Here we show that loss of both copies of hrp36 gene slows down development with significant reduction in adult life span, decreased female fecundity and high sensitivity to starvation and thermal stresses. In the absence of Hrp36, the nucleoplasmic omega speckles are nearly completely disrupted. The levels of nuclear matrix protein Megator and the chromatin remodeller ISWI are significantly elevated in principal cells of larval Malpighian tubules, which also display additional endoreplication cycles and good polytene chromosomes. We suggest that besides the non-coding hsrω-n transcripts, the Hrp36 protein is also a core constituent of omega speckles. The heat-shock-induced association of other hnRNPs at the hsrω locus is affected in hrp36 null cells, which may be one of the reasons for their high sensitivity to cell stress. Therefore, in spite of the functional redundancy provided by Hrp38, Hrp36 is essential for normal development and for survival under conditions of stress.

Public health approach to address maternal mortality.

Reducing maternal mortality is one of the major challenges to health systems worldwide, more so in developing countries that account for nearly 99% of these maternal deaths. Lack of a standard method for reporting of maternal death poses a major hurdle in making global comparisons. Currently much of the focus is on documenting the "number" of maternal deaths and delineating the "medical causes" behind these deaths. There is a need to acknowledge the social correlates of maternal deaths as well. Investigating and in-depth understanding of each maternal death can provide indications on practical ways of addressing the problem. Death of a mother has serious implications for the child as well as other family members and to prevent the same, a comprehensive approach is required. This could include providing essential maternal care, early management of complications and good quality intrapartum care through the involvement of skilled birth attendants. Ensuring the availability, affordability, and accessibility of quality maternal health services, including emergency obstetric care (EmOC) would prove pivotal in reducing the maternal deaths. To increase perceived seriousness of the community regarding maternal health, a well-structured awareness campaign is needed with importance be given to avoid adolescent pregnancy as well. Initiatives like Janani Surakhsha Yojna (JSY) that have the potential to improve maternal health needs to be strengthened. Quality assessments should form an essential part of all services that are directed toward improving maternal health. Further, emphasis needs to be given on research by involving multiple allied partners, with the aim to develop a prioritized, coordinated, and innovative research agenda for women's health.

Topiramate for Migraine Prophylaxis.

Migraine is a significant problem for many children. Topiramate is a newer anticonvulsant and is useful for prophylaxis of adult migraine. This study was conducted to assess efficacy and tolerability of topiramate in pediatric migraine. Topiramate was found to be effective and well-tolerated drug for prophylaxis of pediatric migraine.

Root coverage with free rotated papilla autograft using envelop technique.

Background: Most commonly palatal region is used as the donor site for obtaining connective tissue graft for root coverage as it has the advantage of providing a wide area for obtaining the graft. In the cases requiring small size of graft other intraoral regions can also be used. This is a case report which demonstrates the use of interdental papilla for obtaining connective tissue for root coverage in single teeth in the lower anterior region. Methods: The technique involved creating an envelope in the tissue around the denuded root surface and placing the connective tissue graft taken from the interdental papilla over the recession defect.Result: Clinically significant amount of root coverage was obtained. Conclusion: Root coverage of a shallow narrow recession defect can be obtained with free rotated papilla autograft using envelop technique.