To be Wild or Mutant: Role of Isocitrate Dehydrogenase 1 (IDH1) and 2-Hydroxy Glutarate (2-HG) in Gliomagenesis and Treatment Outcome in Glioma.

Molecular and clinical research based on isocitrate dehydrogenase (IDH) mutations is much sought after in glioma research since a decade of its discovery in 2008. IDH enzyme normally catalyzes isocitrate to α-keto-glutarate (α-KG), but once the gene is mutated it produces an 'oncometabolite', 2-hydroxyglutarate (2-HG). 2-HG is proposed to inhibit α-KG-dependent dioxygenases and also blocks cellular differentiation. Here, we discuss the role of the IDH1 mutation in gliomagenesis. The review also focuses on the effect of 2-HG on glioma epigenetics, the cellular signaling involved in IDH1 mutant glioma cells and the therapeutic response seen in mutant IDH1(mIDH1) harboring glioma patients in comparison to the patients with wild-type IDH1. The review encompasses the debatable impacts of the mutation on immune microenvironment a propos of various mIDH1 inhibitors in practice or in trials. Recent studies revealing the relation of IDH mutation with the immune microenvironment and inflammatory status in untreated versus treated glioblastoma patients are highlighted with respect to prospective therapeutic targets. Also at the molecular level, the association of mIDH1/2-HG with the intracellular components such as mitochondria and other neighboring cells is discussed.

Spinal angiolipoma-a rare but reversible cause of paraplegia in a child.

PURPOSE: Spinal angiolipomas are benign spinal epidural tumors consisting of mature fat cells with angiomatous components. These tumors are rare in children and there are no definite management guidelines. METHOD: To the best of our knowledge, only five cases of spinal angiolipomas have been reported in children below 12 years. This article discusses the presentation, diagnostics, and surgical tips for the management of a case of spinal angiolipoma. RESULT: In this paper, we present a one and half-year-old child presenting with a spontaneous spinal epidural hematoma from a spinal angiolipoma and underscore the importance of early surgery in a benign disease for a good outcome. CONCLUSION: Overall neurological recovery and prognosis following timely intervention for spinal angiolipomas are good.

Palmar arch reconstruction using dorsal venous arch of foot for revascularisation of multiple digits.

A case of trauma causing total loss of superficial and deep palmar arches of hand with ischemia of all the digits was managed using dorsal venous arch of the foot to reconstruct the palmar arch. The ends of the venous arch were anastomosed to radial and ulnar arteries and the tributaries to the arch were coapted to the cut ends of the common digital vessels and princeps pollicis. The surgery yielded gratifying results, successfully revascularising all the digits.

The phylogenetic position of Lepidopygopsis typus (Teleostei: Cyprinidae), a monotypic freshwater fish endemic to the Western Ghats of India.

Lepidopygopsis, known as the peninsular-Indian hill trout, is a monotypic genus endemic to the Periyar stream-reservoir system, in the Western Ghats. Due to the morphological similarity of its only species, L. typus, with the Himalayan schizothoracine fishes, it was considered to be a relict species and a classic example of disjunct distribution. Using mitochondrial and nuclear gene sequence datasets, we show that L. typus is not allied to the schizothoracine fishes. Phylogenetic hypothesis-testing unequivocally supports a scenario in which L. typus and a clade comprising various genera of Asian and African barbins such as Tor Gonoproktopterus, Kosswigobarbus and Varicorhinus are sister groups. Based on our results, we suggest that the sheath of tile-like scales covering the anal-fin base of schizothoracine fishes and Lepidopygopsis typus could be a symplesiomorphy or a homoplasy.

Penile replantation.

Penile amputation is rare and hence the paucity of experience and publication. We present our case of self-inflicted penile amputation, which was successfully managed with microsurgical replantation, with relevant literature review.

Ultra-light-weight microwave X-band EMI shielding or RAM material made from sustainable pyrolysed cork templates.

Cork is a renewable and sustainable material, highly porous and lightweight. We valorised waste cork and recycled wine stoppers to make pyrolysed/carbonised solid cork, for use as economic and sustainable microwave (MW) absorbers at the microwave X-band (8-12 GHz), without binder or additives. Although cork is already a very lightweight material (0.16 g cm-3), the pyrolysed cork is five-times less dense at 0.031 g cm-3, was amorphous graphitic carbon, and had an excellent shielding effectiveness (SET) of -18 to -38 dB, depending on thickness, with attenuation of the electromagnetic energy through internal reflection within the cellular cork structure. Furthermore, this ultra-light-weight material has an extremely high MW specific shielding effectiveness or efficiency (SSE), between -640 to -1235 dB g-1 cm3 over the entire X-band range, depending on thickness (3.0-8.6 mm), one of the highest reported for any pure carbon material, this upper value being more than twice that of any previously reported graphite-based foams.

Negative Pressure Wound Therapy in Surgical Site Infections of Sternotomy Wounds - A Case Series Study in Neonates and Infants.

This case series, performed by the department of plastic and reconstructive surgery at our institution, reports the management of sternal wound dehiscence in newborns and children after cardiac surgery with the help of a negative pressure wound therapy treatment system. Three neonatal patients with poststernotomy wound problems were treated with a negative pressure wound therapy (VAC) system. Negative pressure therapy was started with negative pressure at 50 mm Hg, continuously. All children achieved healing of the sternal wound and a subsequent closure after a mean length of treatment of 33 days (range, 21-49 days). In conclusion, negative pressure therapy with pressure adjusted to lower values as compared with adults in combination with radical surgical debridement was found to be safe and effective, as well as being tolerated well in neonatal and infant patients with extensive or localized poststernotomy wound dehiscence.

Numerical investigation of unruptured middle cerebral artery bifurcation aneurysms: influence of aspect ratio.

An aneurysm is a disease condition, which is due to the pathological weakening of an arterial wall. These aneurysms are often found in various branch points and bifurcations of an artery in the cerebral circulation. Most aneurysms come to medical attention, either due to brain hemorrhages caused by rupture or found unruptured. To consider surgically invasive treatment modalities, clinicians need scientific methods such as, hemodynamic analysis to assess rupture risk. The arterial wall loses its structural integrity when wall shear stress (WSS) and other hemodynamic parameters exceed a certain threshold. In the present study, numerical simulations are carried out for unruptured middle cerebral artery (MCA) aneurysms. Three distinct representative sizes are chosen from a larger patient pool of 26 MCA aneurysms. Logically, these aneurysms represent three growth stages of any patient with similar anatomical structure. Simulations are performed to compare the three growth phases (with different aspect ratios) of an aneurysm and correlate their hemodynamic parameters. Simulations with patient specific boundary conditions reveal that, aneurysms with a higher aspect ratio (AR) correspond to an attendant decrease in both time-averaged wall shear stress (TAWSS) and spatial wall shear stress gradients (WSSG). Smaller MCAs were observed to have higher positive wall shear stress divergence (WSSD), exemplifying the tensile nature of arterial wall stretching. Present study identifies positive wall shear stress divergence (PWSSD) to be a potential biomarker for evaluating the growth of an aneurysm.

Integrated approach for demarcating subsurface pollution and saline water intrusion zones in SIPCOT area: a case study from Cuddalore in Southern India.

This paper deals with a systematic hydrogeological, geophysical, and hydrochemical investigations carried out in SIPCOT area in Southern India to demarcate groundwater pollution and saline intrusion through Uppanar River, which flows parallel to sea coast with high salinity (average TDS 28, 870 mg/l) due to back waters as well as discharge of industrial and domestic effluents. Hydrogeological and geophysical investigations comprising topographic survey, self-potential, multi-electrode resistivity imaging, and water quality monitoring were found the extent of saline water intrusion in the south and pockets of subsurface pollution in the north of the study area. Since the area is beset with highly permeable unconfined quaternary alluvium forming potential aquifer at shallow depth, long-term excessive pumping and influence of the River have led to lowering of the water table and degradation of water quality through increased salinity there by generating reversal of hydraulic gradient in the south. The improper management of industrial wastes and left over chemicals by closed industries has led surface and subsurface pollution in the north of the study area.

1,5-Dimethyl-2-phenyl-4-[phenyl(pyri-din-2-ylamino)methyl]-1H-pyrazol-3(2H)-one.

In the title compound, C(23)H(22)N(4)O, the pyrazole ring makes dihedral angles of 45.57 (11)° with the attached phenyl ring, and 83.98 (10) and 67.85 (10) °, respectively, with the other phenyl ring and the pyridyl ring. The pyridyl ring makes a dihedral angle of 80.15 (10)° with the adjacent phenyl ring. In the crystal, N-H⋯O hydrogen bonds supplemented by weak C-H⋯O hydrogen bonds link the mol-ecules into chains which run parallel to the a-axis direction.

Cu(I)-azidopyrrolo[3,2-d]pyrimidine Catalyzed Glaser-Hay Reaction under Mild Conditions.

The limitation of the CuAAC "click" reaction with a 2-azidopyridine substrate, owing to its equilibrium with a tetrazole isomer, is exploited herein for its utility in the Glaser-Hay reaction. A catalytic combination of a 2-azidopyridine analogue, 4-azido-5H-pyrrolo[3,2-d]pyrimidine, and CuI afforded homocoupled products of terminal alkynes, without any trace of triazole product, under mild conditions with a broad substrate scope. Emphasis on carbohydrate-based substrates appended to a propargylic group led to 1,3-diynes in good to excellent yields.

Alcohol-based hand rub and surgical site infection after elective neurosurgery: an intervention.

BACKGROUND: Controlled studies on the effect of alcohol-based hand rub before and after each patient contact on surgical site infection (SSI) among neurosurgical patients are scarce. Aim : To evaluate the effect of alcohol-based hand rub before and after each patient contact on SSI after elective neurosurgical procedures. SETTING AND DESIGN: Department of Neurosurgery, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Kerala. An intervention study using a 'before-after' design. MATERIAL AND METHODS: Two 9-month study periods were compared; between these periods, an infection-control protocol incorporating an alcohol-based hand rub was implemented for a period of 3 months and continued thereafter. Consecutive patients who underwent neurosurgery between January and September 2006 (control group, before protocol) and between January and September 2007 (intervention group, after protocol) were included. Outcome measures included SSI rates, profile of microorganisms and patient survival. Statistical Analysis : SPSS statistics version 17.0. RESULTS: A total of 1,899 operated cases were reviewed. The patients in the control and intervention groups were similar with regard to sex, age and type of neurosurgery. The surgical site infection rates were 22 (2.3%) out of 974 in the control group and 14 (1.5%) out of 925 in the intervention group (P = 0.2). Patient survival rates were 97.6% (control) and 98.3% (intervention). Post hoc power calculation for an alpha value equal to 0.05, the power obtained was 24.9%, showing inadequacy of sample size to get significant results. To achieve 80% power, the sample size required is about 4,800 each for the control and intervention groups. CONCLUSION: Use of alcohol-based hand rub before and after each patient contact in the neurosurgical intensive care unit did not show a significant reduction in SSI in the present study. This lack of difference between the two groups may be related to the inadequate sample size. The other possibility is that both the strategies are of equal efficacy for prevention of SSIs.

Traumatic Pseudoaneurysm of Anterior Tibial Artery Treated by Thrombin Injection.

Traumatic pseudoaneurysm of limb arteries are relatively rare. A 70-year-old gentleman, with history of mechanical aortic valve implantation on warfarin, presented to the emergency department with pain and swelling in the right leg. He had sustained blunt injury to the leg, a week prior to presentation. On examination, the lateral compartment of the leg was swollen, ecchymotic, and tense. Distal pulses were well palpable. An ultrasound Doppler evaluation revealed a large intramuscular hematoma in the lateral compartment with a pseudoaneurysm of a muscular branch of the anterior tibial artery. An ultrasound-guided compression of the pseudoaneurysm was initially attempted for 24 hours, which failed in closing off the pseudoaneurysm. He was subsequently taken up for thrombin injection into the pseudoaneurysm, which resulted in instant thrombosis of the pseudoaneurysm, with an uneventful clinical course thereafter. Thrombin injection is an effective and safe modality to treat pseudoaneurysms of limb arteries.

Giant Cavernomas: Gigantic Propositions for a Lilliputian Problem?

AIM: The aim of this case series is to report two cases of giant cavernomas treated at a tertiary level centre along with a literature review on the differences between giant cavernomas and normal sized cavernomas. METHOD: The first case was that of a 13-year-old male with habitual seizures since one year of age with normal examination findings. His imaging revealed a large parieto-occipital lesion which was excised microsurgically after a parieto-occipital craniotomy and a transcortical approach. The second case was a 26-year-old male who presented with generalised seizures and bilateral visual loss. Imaging was suggestive of a large left lateral ventricular lesion. A left fronto-temporo-parietal craniotomy was done followed by transventricular microsurgical excision. Histopathology of both cases were reported to be cavernomas. The first patient had transient hemiparesis post-operatively which improved within 24 hours. Eventually, both patients had an uneventful follow-up. CONCLUSION: Microsurgical excision remains the treatment of choice for giant cavernomas. In toto excision may be advocated depending upon the location of the cavernoma especially with respect to eloquence and venous anatomy.

MutT Homolog1 has multifaceted role in glioma and is under the apparent orchestration by Hypoxia Inducible factor1 alpha.

AIMS: The study focused on the expression and role of a recent potential cancer therapeutic target protein, MutT Homolog1 (MTH1). MTH1 gets activated in an increased reactive oxygen species (ROS) environment and removes the oxidized nucleotides from the cell. The study aimed to check the role of MTH1 in DNA damage and apoptosis, migration and angiogenesis and also to examine its regulation in glioma. MAIN METHODS: The experiments were carried out in human glioma tissue samples and brain tissues of epilepsy patients (non-tumor control). We used two human glioblastomas cell lines, U87MG and U251MG cells. In order to study the role of MTH1 in glioma and to analyze the relation of MTH1 with Hif1α, we have used MTH1 siRNA and Hif1α siRNA respectively. KEY FINDINGS: We found an increased expression of MTH1 in glioma tissues compared to the non-tumor brain tissues. Correlation analysis revealed that those samples showing reduced expression of MTH1 also had high levels of DNA damage and apoptotic markers, while diminished expression of angiogenesis regulators and levels of migration. MTH1 knockdown in vitro by siRNA in tumor cell lines corroborates the above observation. This justifies the emergence of MTH1 inhibitors as potential first-in-class drugs. Mechanistically, our observations suggest that Hif1α may modulate MTH1 expression. SIGNIFICANCE: We found elevated MTH1 expression in glioma irrespective of their grades, while its inhibition affects multiple tumor progression pathways, and that targeting Hif1α could simulate the same.

Five-year mortality and readmission rates in patients with heart failure in India: Results from the Trivandrum heart failure registry.

INTRODUCTION: Heart failure (HF) has emerged as an important and increasing disease burden in India. We present the 5-year outcomes of patients hospitalized for HF in India. METHODS: The Trivandrum Heart Failure Registry (THFR) recruited consecutive patients admitted for acute HF among 16 hospitals in Trivandrum, Kerala in 2013. Guideline-directed medical therapy (GDMT) was defined as the combination of beta-blockers (BB), renin angiotensin system blockers (RAS), and mineralocorticoid receptor antagonists (MRA) in patients with HF with reduced ejection fraction (HFrEF, EF < 40%) at discharge. We used Cox proportional hazards models and Kaplan-Meier survival plots for analysis. The MAGGIC risk score variables were included as exposure variables. RESULTS: Among 1205 patients [69% male, mean (SD) age = 61.2 (13.7) years], HFrEF constituted 62% of patients and among them, 25% received GDMT. The 5-year mortality rate was 59% (n = 709 deaths), and median survival was 3.1 years. Sudden cardiac death and pump failure caused 46% and 49% of the deaths, respectively. In the multivariate Cox model, components of GDMT associated with lower 5-year mortality risks were discharge prescription of BB, RAS blocker, and MRA. Older age, lower systolic blood pressure, NYHA class III or IV, and higher serum creatinine were also associated with higher 5-year mortality. CONCLUSIONS: Three out of every 5 patients had died during 5-years of follow-up with a median survival of approximately 3 years. Lack of GDMT in patients with HFrEF and frequent readmissions were associated with higher 5-year mortality. Quality improvement programmes with strategies to improve adherence to GDMT and reduction in readmissions may improve HF outcomes in this region.

Bilateral thalamic lesions.

OBJECTIVE: Bilateral thalamic lesions are rare and relatively obscure neoplasms. We present our experience with nine cases of bilateral thalamic lesions and attempt to analyse them in the background of available literature. MATERIALS AND METHODS: Retrospective analyses of the case records of 9 cases of bilateral thalamic lesions treated in our department since January 2002, which have a minimum of 1 year follow-up. RESULTS: The study group included four males and five females with a mean age of 14.6 years (5 years to 29 years). Seven of these patients had radiological evidence of bilateral thalamic lesions at presentation and 2 patients had involvement of the opposite thalamus at a later stage of the disease. All patients except one presented with raised intracranial pressure symptoms. Focal motor deficits (4/9), behavioral and memory disturbances (3/9) were the other major presenting symptoms. Biopsy confirmation was possible in six patients and histopathology was suggestive of low grade fibrillary astrocytoma in all six patients. Seven patients required CSF diversion procedure for associated hydrocephalus. Eight of our nine patients underwent radiotherapy. On last follow-up, 3 patients were clinically stable with images suggestive of arrested disease, four patients had evidence of progressive disease both clinically and radiologically and there were two recorded cases of mortality. CONCLUSION: Primary bilateral thalamic lesions have characteristic neuroradiological properties and are distinct from unilateral thalamic tumours with bilateral progression. Almost all of these lesions on histology prove to be gliomas but decompressive surgery is seldom feasible. Surgical intervention is limited to biopsy and CSF diversion for hydrocephalus. Bilateral thalamic lesions remain unresponsive to adjuvant therapy and generally carry a poor prognosis.

Choroid plexus tumors: an institutional series of 25 patients.

PURPOSE: Choroid plexus tumors (CPT) are rare neoplasms that pose considerable treatment challenges. This study reviews a single institute's experience with 25 patients of CPT and attempts to contribute to the general body of knowledge on CPT. MATERIALS AND METHODS: A retrospective analysis of the case records of 25 patients operated for CPT since January 1998 and having a minimum of 1 year follow-up. RESULTS: The study group included 12 (48%) cases of choroid plexus papilloma (CPP), 09 (36%) cases of choroid plexus carcinoma (CPC) and 4 cases of atypical CPP. The mean age at presentation was 18.6 years (range, 6 months to 54 years; SD, 18.7) and a male preponderance was noted (17:8). Raised intracranial pressure was the commonest presenting symptom (72%). The tumors were distributed as follows: lateral ventricle (16; 64%), fourth ventricle (5; 20%), fourth ventricle with cerebellopontine angle extension (3; 12%), and third ventricle (1; 4%). A complete surgical excision was achieved in 11 cases of CPP and 8 cases of CPC. Operative complications include pneumocephalus (40%), focal deficits (36%), subdural effusion (32%), and persistent hydrocephalus requiring shunt (24%). All patients with CPP had a good outcome at the end of a mean follow-up of 5.4 years, whereas the median survival for patients with CPCs who underwent a subtotal resection with adjuvant therapy was 36 months. CONCLUSION: CPTs include a spectra ranging from CPP to CPC. Radiologic and histologic characterization of these tumors is difficult and newer immunohistochemical and genetic studies should be done to differentiate them from each other. Total excision offers a good prognosis and should be attempted for all forms of CPTs. CPPs carry a good prognosis, and adjuvant therapy is not indicated even after partial excision. CPCs and atypical CPCs carry a poor prognosis, and adjuvant therapy improves survival marginally after total excision. Spinal drop metastases are common for CPC and screening of the spine for possible metastasis should be part of the routine preoperative and postoperative investigation protocol.

Oral health care system analysis: A case study from India.

OBJECTIVES: The health system of Kerala, India has won many accolades in having health indicators comparable to developed countries. But oral health has not received its due importance at the policy level. With the burden of oral diseases on the rise in the state, a critical introspection of the existing system is warranted. The objective of this review was to assess the oral health care system in Kerala to provide policy solutions. METHODS: This study adopted a mixed methodological approach that gathered information from the primary and secondary sources, which included health facility surveys, key informant interviews, review of published literature, and websites of governmental and non-governmental bodies. The WHO framework of health system building blocks was adapted for the assessment. RESULTS: A review of epidemiological studies conducted in Kerala suggests that the prevalence of oral diseases is high with the prevalence of dental caries at the age of 12 years ranging from 37-69%. The state has a dentist population ratio of 1:2200 which is well within the prescribed ratio by WHO (1:7500). Only 2% of dentists in Kerala work with government sector catering to 0.6 million of the approximately 33.4 million population. This point to the absence of oral care in first contact levels like primary health centers. Service delivery is chiefly through the private sector and payment for dental care is predominantly through out-of-pocket expenditure. CONCLUSION: Despite having the best health indicators, the oral health system of Kerala is deficient in many aspects. Reorientation of oral health services is required to combat the burden of diseases.