Tudor tells about new twists in the story tale of SMURFs.

Smad ubiquitin regulatory factors (SMURFS) belong to the HECT- family of E3 ubiquitin ligases. This family has two members, SMURF1 and SMURF2. SMURFs have emerged as well studied negative regulators of TGF induced intracellular signaling. However, increasingly it is being realized that SMURFs tactfully modulate an array of proteins in different cancers. This review sets spotlight on how SMURF1 and SMURF2 communicate with effectors of different signaling pathways during the multistep progression to cancer. We also summarize how microRNAs (miRNAs) effectively control SMURFs in different cancers. Role of SMURFs is context dependent in different cancers and better concepts related to miRNA regulation of SMURFs in different stages and steps of cancer will be helpful in efficient translation of laboratory findings to clinic.

How sesquiterpenes modulate signaling cascades in cancers.

Data obtained from high-throughput technologies has started to shed light on the interplay between signal transduction cascades and chromatin modifications thus adding another layer of complexity to the already complex regulation of the protein network. Based on the insights gleaned from almost a decade of research, it has now been convincingly revealed that sesquiterpenes effectively modulated different intracellular signaling cascades in different cancers. In this review we summarize how sesquiterpenes mediated Wnt, Shh, Notch and TRAIL induced signaling cascades.

Impact of genetic variants of RFC1, DHFR and MTHFR in osteosarcoma patients treated with high-dose methotrexate.

Osteosarcoma patients are commonly treated with high doses of methotrexate (MTX). MTX is an analog of folate, which is essential for DNA synthesis. Genetic polymorphism at single nucleotide can be indicative to the prognostic outcome in patients. Germ-line variants in candidate genes, coding for enzymes active in the metabolism of MTX, were studied in 62 osteosarcoma patients. Patients harboring the GG genotype in reduced folate carrier 1 (RFC1) rs1051266 had significantly better survival in comparison with patients having the AA genotype (P=0.046). These patients also had a lower frequency of metastasis (15%, P=0.029). Also patients homozygous for the G allele of rs1053129 in the dihydrofolate reductase (DHFR) gene were more likely to have a metastasis (45%, P= 0.005), and the methylenetetetrahydrofolate reductase (MTHFR) 677C allele was associated with higher degree of liver toxicity (88%, P=0.007). The study suggests that germ-line variants in the MTX metabolic pathway are associated with survival and side effects in patients treated with MTX.

Incidence of post obturation pain following single and multi visit root canal treatment in a teaching hospital of Bangladesh.

Post obturation pain is the pain of any degree after endodontic treatment. There are different opinions regarding incidence of post obturation pain related to single and multi visit root canal treatment. This prospective study was conducted to evaluate the incidence of post obturation pain in single visit and multi visit root canal treatment and to compare the incidence of pain between the two treatment groups. A total of 120 cases of endodontically involved asymptomatic non vital single rooted teeth were selected for this study. The patients were assigned and divided in to two treatment groups, sixty patients each. In single visit group, all teeth were prepared and filled using the standardized preparation and lateral condensation filling technique. In the multi visit treatment group, at the first appointment, the teeth were prepared, and dressed with calcium hydroxide paste for 7 days. At the second appointment, the teeth were prepared and obturated by using lateral condensation technique. The frequency of post obturation pain was recorded as no pain, slight, moderate and severe pain and evaluated at the day 1 and at the day 7 after obturation. The data were analyzed statistically by using SPSS version-12. P value <0.05 was taken as significant. The study showed that the post obturation pain in the single visit treatment group was more than multi visit treatment group, which is significant (p value <0.044). Out of the 120 patients, 86(71.7%) patients had no pain, 19(15.8%) had slight pain and 15(12.5%) patients had moderate pain at the day 1 after obturation. At the day 7 after obturation, 108(90%) patients had no pain, 9(7.5%) had slight pain and 3(2.5%) patients had moderate pain. No patient noticed severe pain during the follow up period. Older patient had significantly more post obturation pain than the younger patient. There was higher incidence of post obturation pain following the single visit root canal treatment. In multi visit root canal treatment with intra-canal medicaments seems to reduce the post obturation pain.

Measuring the effectiveness of an integrated intervention package to improve the level of infection prevention and control: a multi-centre study in Bangladesh.

BACKGROUND: Infection prevention and control (IPC) is a critical component of delivering safe, effective and high-quality healthcare services, and eliminating avoidable healthcare-associated infections (HAIs) in health facilities, predominantly in population-dense settings such as Bangladesh. AIM: Our study aimed to assess the effect of an integrated intervention package in improving the IPC level of the health facilities in Bangladesh. METHODS: We conducted a pre-post intervention study in six district hospitals (DHs) and 13 Upazila Health Complexes (UHCs) in the six districts of Bangladesh. Baseline and endline assessments were conducted between March and December 2021 using the adapted World Health Organization Infection Prevention and Control Assessment Framework (WHO-IPCAF) tool. The IPCAF score, ranging from 0-800, was calculated by adding the scores of eight components, and the IPC promotion and practice level was categorized as Inadequate (0-200), Basic (201-400), Intermediate (401-600) and Advanced (601-800). The integrated intervention package including IPC committee formation, healthcare provider training, logistics provision, necessary guidelines distribution, triage/flu corners establishment, and infrastructure development was implemented in all facilities. RESULTS: The average IPCAF score across all the facilities showed a significant increase from 16% (95% CI: 11.5-20.65%) to 54% (95% CI: 51.4-57.1%). Overall, the IPCAF score increased by 34 percentage points (P<0.001) in DHs and 40 percentage points (P<0.001) in UHCs. Following the intervention, 12 (three DHs, nine UHCs) of 19 facilities progressed from inadequate to intermediate, and another three DHs upgraded from basic to intermediate in terms of IPC level. CONCLUSION: The integrated intervention package improved IPCAF score in all facilities.

Magnetic Resonance Imaging Evaluation of Common Spinal Intramedullary Tumours: Ependymoma and Astrocytoma.

This cross-sectional study was carried out in the Department of Radiology and Imaging, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from January 2015 to June 2016 in collaboration with Department of Neurosurgery and Department of Pathology of same hospital, to assess MRI findings of common IMSCTs and to find out the validity of MRI in the diagnosis of spinal ependymoma and astrocytoma, thereby differentiating these two common intramedullary entities. For this purpose, 40 patients aged from 15 to 60 years, who were diagnosed or suspected cases of having intramedullary spinal cord tumours were enrolled. These patients underwent preoperative MRI for evaluation of the spinal cord tumours during the study period in department of Radiology and Imaging. Also, patients were diagnosed by MRI as having IMSCTs incidentally was included. All of them were followed by histopathological examination of the same lesions after surgery. Among these 40 patients after exclusion for valid reason 28 cases were included as study population. MR images were obtained on a 1.5 Tesla (Avanto Magnatom, Siemens) unit with a spine surface coil. MRI findings were compared with histopathology after surgery keeping histopathology as gold standard. Out of 28 clinically and MRI diagnosed IMSCTs cases, 19 cases of ependymoma, 8 cases of astrocytoma and one diagnosed as hemangioblastoma by MRI. The mean age was 34.11±9.55 years, ranging from 15 to 56 years for ependymoma, 26.88±8.08 years ranging from 16 to 44 years for astrocytoma. Highest incidence (47.4%) was in between 31 to 40 years for ependymoma, 50.0% were in between 21-30 for Astrocytoma. On MRI majority 12(63.2%) of the cord ependymomas and majority 5(62.5%) of astrocytomas were in cervical region. While considering axial location ependymomas are mostly 17(89.5%) central and astrocytomas 5(62.5%) are eccentric in location. It was observed that out of 19 cases of ependymoma more than half 10(52.6%) had elongated shape, 12(63.1%) had well defined margin. Associated syringohydromyelia was present in 16(84.2%) cases. On T1WI 11(57.9%) and 8(42.1%) cases were iso and hypo respectively. On T2WI 14(73.7%) cases were hyper intense. After Gd-DTPA in most cases, 13(68.4%) cases showed diffuse enhancement. Noticeable and sizeable solid component observed among 13(68.4%) of the cases. Hemorrhage with cap sign was found in more than one third 7(36.8%) cases. Out of 8 cases of astrocytomas 4(50.0%) had lobulated shape, ill-defined margin 5(62.5%). T1WI: Iso 5(62.5%), hypo 3(37.5%), T2WI: hyper 5(62.5%), After Gd-DTPA: focal and heterogenous enhancement 3(37.5%) and rim enhancement 4(50.0%). Component: mixed 4(50.0%), cystic 3(37.5%) and solid 1(12.5%). Hemorrhage without cap sign 2(25.0%), associated syringohydromyelia 1(12.5%). In the case of evaluation of intramedullary ependymoma sensitivity of MRI in the present series is 94.44%, specificity 80.0%, Positive predictive value (PPV) 89.5%, Negative predictive value (NPV) 88.9% and accuracy 89.28%. In case of MRI evaluation of intramedullary astrocytoma sensitivity of MRI in the present study is 85.71%, specificity 90.47%, PPV 75%, NPV 95% and accuracy 89.2%. Thus present study shows MRI is a sensitive and effective noninvasive imaging modality in diagnosing common intramedullary spinal cord tumours.

Ultra-sculpturing of seed morphotypes in selected species of genus Salvia L. and their taxonomic significance.

The taxonomic importance of macromorphological and micromorphological seed characteristics was investigated using SEM of ten species of the Salvia genus from Pakistan. The aim was to identify diagnostic seed ultrastructural features that could aid in species delimitation, correct identification and phylogenetic position. The ultrastructure of Salvia varies greatly, and a wide range of unique micromorphological features have been observed. Seed micromorphological features were explored by SEM, including seed shape, colour, texture, cell outline, surface sculpturing, epidermal cell arrangement, anticlinal, and periclinal wall pattern. Seed shapes were categorized as obovate, spherical, spheroid, broadly elliptic, elliptic and oblong, mostly with a terminal hilum. Seed colours were black, light brown, dark brown, brown and yellow. Exo-morphological characters, i.e. epidermal cell arrangements, included irregular, wavy pentagonal-hexagonal, regular pentagonal-hexagonal. Cluster analysis was used to assess similar and distinct species within Salvia with a feasible explanation. Taxonomic keys were made based on micromorphological qualitative features that help to delimit species and identify them quickly within the Salvia genus. Seed morphology of ten Salvia species was described and investigated, and the diagnostic significance of features evaluated using SEM. This study analysed seed features, especially at the species level, which might provide much new taxonomic information. The results revealed that, in seed morphology, using SEM can help with taxon identification, especially at the genus and species levels.

Diagnostic Accuracy of Magnetic Resonance Imaging in Evaluation of Anterior Cruciate Ligament Tear.

The anterior cruciate ligament (ACL) is the most generally injured one of the major knee ligaments. These injuries plague both athletes and non-athletes. This cross-sectional and comprehensive study was conducted in the Department of Radiology and Imaging collaborating with Department of Orthopedics of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, completed from January 2014 to December 2015. The study evaluated the role of MRI in the diagnosis of anterior cruciate ligament injury of knee joint, keeping Arthroscopy as standard, compared the MRI and arthroscopic findings to determine accuracy, sensitivity and predictivity of MRI in the diagnosis of ACL injury in knee joint. For this purpose, a total of 50 patients having clinical suspicion of ACL injury in knee joint were enrolled in this study to perform MRI and Arthroscopy. MRI was done in all these patients. Clinically suspected but MRI diagnosed as no ACL injury, patients who were not willing to undergo arthroscopy examination and patient who were not fit for arthroscopy were excluded from the study. More than half (52.0%) of the patients were in 3rd decade and male to female ratio was 3.5:1. Less than one fourth (24.0%) of the patients were service holder. Forty two percent patients had duration of suffering for 2 weeks. Most 49(98.2%) patients had history of trauma, 45(90.0%) had pain in Knee joint, 24(48.0%) had difficulty in walking, 19(38.0%) had swelling in Knee joint and 13(26.0%) had restricted range of motion. Anterior drawer test was 37(74.0%) and Lachman test 16(32.0%). Loss of normal contour of ACL was found in 50.0%. Signal change of ACL in PD and T2W1 was found 42(84.0%) patients, and thickened ACL in 33(66.0%) patients. In MRI diagnosis tear was present in 80.0% of the patients. ACL tear diagnosed by MRI among the patients, 20(40.0%) had partial tear and 20(40.0%) had complete tear. In arthroscopy diagnosis 38(76.0%) had tear present. ACL tear diagnosed by arthroscopy of the patients 15(30.0%) had partial tear and 23(46.0%) had complete tear. Majority 20(40.0%) patients had medial meniscus injury, 15(30.0%) had lateral meniscus injury, 11(22.0%) had PCL injury, 4(8.0%) had lateral co-lateral ligament injury and 2(4.0%) had medial co-lateral ligament injury. In MRI diagnosis of anterior cruciate ligament tear, 37 cases were true positive, three cases false positive, one case false negative and nine cases was true negative. The validity of MRI diagnosis evaluation for anterior cruciate ligament tear was 97.4% sensitivity, 75.0% specificity, 92.0% accuracy, 92.5% positive predictive values and 90.0% negative predictive values.

Detection of bacterial blight resistance genes in basmati rice landraces.

Aromatic basmati rice is vulnerable to bacterial blight disease. Genes conferring resistance to bacterial blight have been identified in coarse rice; however, their incorporation into basmati varieties compromises the prized basmati aroma. We identified bacterial blight resistance genes Xa4, xa5, Xa7, and xa13 in 52 basmati landraces and five basmati cultivars using PCR markers. The Xa7 gene was found to be the most prevalent among the cultivars and landraces. The cultivars Basmati-385 and Basmati-2000 also contained the Xa4 gene; however, xa5 and xa13 were confined to landraces only. Ten landraces were found to have multiple resistance genes. Landraces Basmati-106, Basmati-189 and Basmati-208 contained Xa4 and Xa7 genes. Whereas, landraces Basmati-122, Basmati-427, Basmati-433 were observed to have xa5 and Xa7 genes. Landraces Basmati-48, Basmati-51A, Basmati-334, and Basmati-370A possessed Xa7 and xa13 genes. The use of landraces containing recessive genes xa5 and xa13 as donor parents in hybridization with cultivars Basmati-385 and Basmati-2000, which contain the genes Xa4 and Xa7, will expedite efforts to develop bacterial blight-resistant basmati rice cultivars through marker assisted selection, based on a pyramiding approach, without compromising aroma and grain quality.

Risk factors, clinical profile, and long-term outcome of 428 patients of cerebral sinus venous thrombosis: insights from Nizam's Institute Venous Stroke Registry, Hyderabad (India).

BACKGROUND: With the widespread use of neuroimaging and hematological workup, many of the previously held concepts about cerebral sinus venous thrombosis (CSVT) are changing. OBJECTIVE: The objective of this study was to investigate the risk factors, clinical profile, and outcome of the fully investigated cases of CSVT from a major university referral hospital in South India. MATERIALS AND METHODS: Consecutive patients of CSVT confirmed by definite neuroimaging criteria and fully investigated for prothrombotic states, between June 2002 and September 2010, were prospectively studied in the Venous Stroke Registry of Nizam's Institute of Medical Sciences, Hyderabad, South India. RESULTS: Of the 428 patients, 230 (53.7%) were men and the mean age was 31.3 years (range 8-65 years). Seizures were noted in 126 (29.4%) patients, stroke like presentation was found in 122 (28.5%) patients, and benign intracranial hypertension like presentation was found in 78 (18.2%) patients. Common risk factors were anemia in 79 (18.4%), hyperhomocysteinemia in 78 (18.2%), alcoholism in 67 (15.6%), oral contraceptive pill intake in 49 (11.4%), postpartum state in 42 (9.8%), anticardiolipin antibodies in 31 (7.2%), and protein S deficiency in 53 (12.3%) patients. Good outcome at 90 days (modified Rankin Scale £ 2) was observed in 273 (71.2%) of 383 patients available for follow-up. In-house mortality was noted in 33 (7.7%) and recurrence in 22 (5.1%) patients. CONCLUSIONS: Compared to the previous studies, prevalence of CSVT was higher in men. Anemia, hyperhomocysteinemia, alcoholism, oral contraceptive use, and postpartum state were the most common risk factors. Overall prognosis was good, but a small percentage of patients died or showed recurrence.

Role of Dynamic Magnetic Resonance Imaging in Hirayama Disease, a Rare Motor Neuron Disease.

Introduction Hirayama disease (HD) is a benign self-limiting motor neuron disease, most commonly occurring in young males. The disease has an insidious onset that affects T1, C8, and C7 myotomes. HD is more common in Japan and Asian countries, and rare in the western population. Magnetic resonance imaging (MRI) is the best technique for the diagnosis of this entity. Early diagnosis is important as the patients can be advised to limit neck flexion movements to arrest the progression of the disease. Any clinically suspected case of Hirayama disease should undergo flexion MRI as conventional neutral MRI may miss findings in a few cases. The purpose of the present study is to evaluate the usefulness of flexion MR imaging and laminodural space (LDS) measurement in young patients with clinical and electroneuromyography (ENMG) definite Hirayama disease. Materials and methods This is a retrospective observational study of 15 patients with clinical and ENMG definite Hirayama disease who were referred to the Department of Radiology. These patients underwent MRI of cervical spine in neutral position and with neck flexion of 30°-40°. In neutral MRI, atrophy and T2-weighted hyperintensities in the cord were noted. In flexion MRI, the maximum forward shifting of the posterior dural sac, also known as the LDS, was noted along with other parameters. Observation The mean age of the study population was 21 ± 3.36 years. Out of 15 patients, 14 were males and one was female; 14 patients (93.3%) had an involvement of unilateral upper extremity while one patient (6.6%) had asymmetric bilateral involvement. Straightening of cervical spinal curvature and cord atrophy was seen in 14 (93.3%) and 12 (80%) patients, respectively, on neutral position MRI. Intramedullary cervical cord T2-weighted hyperintensities were noted in eight patients (53.3%). Loss of the dural attachment and forward shifting of the posterior dural sac with prominent posterior epidural space was noted in all patients (100%). At the maximum forward shift of cord, the LDS ranged from 3.1 to 7.0 mm, with a mean of 5.38 ± 1.13 mm. Epidural flow voids were noted in 86.6% of cases. Conclusion Flexion MRI plays a very important role in confirming the diagnosis of Hirayama disease in clinically suspected cases. Anterior displacement of posterior dura matter and widening of LDS is noted in all cases in our study. Even though findings like cord atrophy and T2 hyperintensities are seen in conventional neutral MRI, these findings are not seen in all cases. So flexion MRI increases diagnostic confidence by showing increased LDS, which is a characteristic finding in Hirayama disease.

Four new nodulose-spored species of Inocybe (Agaricales) from West Africa.

We describe four new nodulose-spored species of Inocybe from tropical regions of Africa: I. beninensis, I. flavipes, I. fuscobrunnea and I. pallidiangulata. The new species are recognised based on morphological data and phylogenetic analyses of ITS, 28S and RPB2 sequences. Phylogenetic analyses indicated that I. flavipes and I. beninensis are part of a subclade leading to the I. calida group. Inocybe fuscobrunnea appears sister to the I. asterospora group. Inocybe pallidiangulata is nested within a clade of mainly tropical species from South Asia, Africa, and South America, close to the subclade of I. lilacinosquamosa and I. ayangannae from Guyana. Complete descriptions and illustrations, including photographs and line drawings, and a key to nodulose-spored taxa of tropical African species of Inocybe are provided. Citation: Aïgnon HL, Jabeen S, Verbeken A, Matheny PB, Yorou NS, Ryberg M (2022). Four new nodulose-spored species of Inocybe (Agaricales) from West Africa. Fungal Systematics and Evolution 10: 1-18. doi: 10.3114/fuse.2022.10.01.

Clinical, electrophysiological subtypes and antiganglioside antibodies in childhood Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré syndrome (GBS) has been the most common cause of flaccid paralysis in children after the decline in the incidence of poliomyelitis. There are not any published data from the Indian subcontinent documenting electrophysiological patterns and antiganglioside antibodies in pediatric GBS. MATERIALS AND METHODS: The study population included children with GBS referred for electrodiagnostic evaluation and also children with GBS admitted to our institute between August 2006 and July 2007. Nerve conduction studies were done to determine GBS subtypes and serum antiganglioside antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Clinical and electrophysiological features were correlated with antiganglioside antibody results. RESULTS: Of the 43 (male to female ratio = 2.1:1) children studied, 97.6% had motor weakness, 76.7% had cranial nerve palsies, 13.9% had autonomic disturbances and respiratory paralysis was found in 9.3% children. Antecedent illness was recorded in 69.8% children. The GBS subtype distribution was as follows: acute inflammatory demyelinating polyradiculoneuropathy (AIDP) in 21 (48.8%), acute motor axonal neuropathy (AMAN) in 19 (44.2%), and 3 (6.9%) children were unclassified. The severity of illness was similar in both AMAN and AIDP subtypes and the recovery in both the subtypes was complete without any significant difference in the duration of recovery. Preceding diarrheal illness was more common in AMAN subtype as compared to AIDP subtype (57.9% vs. 4.7%, P = 0.007). Sensory symptoms were more common in AIDP subtype than in AMAN subtype (66.6% vs. 21%, P = 0.03}. The commonest ganglioside antibody was IgM GM2. Anti GM3 antibodies were exclusively seen in children with AMAN and IgG GD1b was significantly associated with (36.7 vs. 4%; P = 0.007) AMAN subtype. IgG GT1b was identified in 50% of patients with AIDP as compared to 22.7% in patients with AMAN. CONCLUSION: In this study, AMAN subtype accounted for a significant proportion of pediatric GBS. AMAN was associated with diarrhea and specific antiganglioside antibodies. Recovery in children with GBS was complete, irrespective of the subtype.

Effect of peripheral kisspeptin administration on adiponectin, leptin, and resistin secretion under fed and fasting conditions in the adult male rhesus monkey (Macaca mulatta).

In the last few years, kisspeptin-KISS1R signaling has appeared as a major regulator of the reproductive function in several vertebrate species. However, KISS1(encoding kisspeptin) and its putative receptor, KISS1R, are expressed in several other tissues. Adipose tissue, which secretes many peptides with diverse functions in normal physiology, expresses KISS1, which is modulated by gonadal steroids as well as by body nutritional status. Similarly, KISS1Rexpression is also found in adipose tissue, but the local role of kisspeptin in adipocyte function is currently unknown. Therefore, in the present study the effects of exogenous human kisspeptin-10 (KP10) were studied on three important adipokines, namely, adiponectin, leptin, and resistin in a set of four chair-restraint habituated intact adult male rhesus monkeys under; 1) normal fed conditions, 2) 24-h fasting conditions, and 3) 48-h fasting conditions. Plasma resistin and leptin levels decreased (p<0.01), whereas adiponectin levels increased (p<0.05) in fasted monkeys. Kisspeptin administration significantly increased (p<0.05) mean plasma adiponectin levels under fed and 24-h fasting conditions as compared to pretreatment or vehicle-treatment levels. A stimulatory effect was also observed on the 48-h fasting stimulated plasma adiponectin levels, but it lacked statistical significance. In contrast, no effect of kisspeptin was observed on mean plasma leptin and resistin levels. Thus, the present study demonstrated a stimulatory effect of peripheral kisspeptin administration on the plasma adiponectin levels under fed and 24-h fasting conditions in the adult male rhesus monkey. These findings, therefore, assign a novel role to kisspeptin, a regulator of adipocyte function in higher primate.

Predictors of major neurological improvement after intravenous thrombolysis in acute ischemic stroke: a hospital-based study from south India.

BACKGROUND: Despite the increasing use of recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke, uncertainty persists about the short- and long-term outcome of the thrombolysed patients. OBJECTIVE: To identify predictors of major neurological improvement at 24 h after intravenous rt-PA administration in patients of acute ischemic stroke and their relationship with outcome at 12 months. MATERIALS AND METHODS: We analyzed the data of the patients with acute ischemic stroke treated as per the National Institute of Neurological Disorders and Stroke (NINDS) criteria with intravenous rt-PA between January 2000 and June 2009 at a tertiary care center in south India. Major neurological improvement was defined by an 8-point improvement in National Institute of Health Stroke Scale (NIHSS) score or an NIHSS score of 0 or 1 at 24 h. Good outcome was defined as a 12-month modified Rankin Scale (mRS) of 0 to 1. RESULTS: Of the 72 patients with acute ischemic stroke treated with intravenous rt-PA, 23 (32%) patients had major neurological improvement at 24 h. Age <60 years (OR 1.9, 95% CI 1.7 to 3.2), admission glucose levels <8 mmol/L (OR 3.87, 95% CI 1.9 to 9.2) and mild to moderate baseline stroke severity (NIHSS median score 10+ 6) were associated with major neurological improvement after adjusting for co variables. Major neurological improvement at 24 h was an independent predictor of good outcome (mRS=1) at 12 months (OR 13.9, 95% CI 6.84 to 40.2). CONCLUSIONS: Age <60 years, glucose levels <8 mmol/L and mild to moderate stroke severity (NIHSS median score 10+/-6) was associated with major neurological improvement after intravenous rt-PA. Major neurological improvement at 24 h after the administration of intravenous thrombolysis independently predicted good outcome at 12 months.

Functional Outcome of Bilateral Subthalamic Nucleus-Deep Brain Stimulation in Advanced Parkinson's Disease Patients: A Prospective Study.

BACKGROUND: Deep brain stimulation (DBS) is an accepted modality of treatment in patients with Parkinson's disease (PD). Although DBS was approved in advanced PD, it is being done in early PD as well. It was mainly developed to help the patients of PD to overcome the adverse motor effects associated with treatment and treatment failure. OBJECTIVE: The objective is to study the efficacy of subthalamic nucleus (STN)-DBS procedure in patients with PD. MATERIALS AND METHODS: This was a prospective, single-center, follow-up observational study using a direct, structured interview of 40 selected PD patients. Preoperative assessment using Unified PD Rating Scale-III (UPDRS-III), Montreal Cognitive Assessment (MOCA), and Parkinson's Disease Questionnaire-39 were done. All the patients underwent DBS. Postoperatively, similar assessment was done during follow-up period of 6 months. The results were analyzed using Student's t-test. RESULTS: The total score of UPDRS-III was reduced by 35% after STN-DBS intervention which was statistically significant (P < 0.05). STN-DBS intervention was successful in significantly reducing all UPDRS-III subscores but failed to reduce the scores in case of postural stability. MOCA scores of the patients were not found to be affected by STN-DBS intervention (P = 0.1466). Similar findings were also observed for MOCA subscores, but there was significant improvement of verbal fluency in all patients. Quality of life(QoL) improved significantly in all patients after STN-DBS intervention in all areas. Lower baseline UPDRS-III scores were found to enhance the QoL both in "off" and "on" state. However, prolonged disease duration and older age at PD onset were found to be hampering factors in the improvement of QoL. CONCLUSIONS: STN-DBS is a safe procedure and can be performed in all patients of PD who develop disabling motor fluctuations to improve their QoL irrespective early or advanced disease.

The Effect of Dual Tasking and Deep Brain Stimulation Frequency Parameters on Gait in Advanced Parkinson's Disease.

OBJECTIVE: To study the effect of dual tasking and deep brain stimulation frequency parameters on gait in advanced Parkinson's disease. MATERIALS AND METHODS: This is an open label interventional study evaluating 40 post STN-DBS patients with gait disturbances. All patients were diagnosed as PD by a movement disorder specialist using the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) criteria. Patients underwent bilateral subthalamic deep brain stimulation by a qualified neurosurgeon. Patients were managed on a combination of dopamine replacement therapy as well as deep brain stimulation. Patients were assessed by stand walk sit (SWS) test for a 5 meter distance and FOG scoring during medication 'ON' state and device "ON" state, at four frequencies 180, 130, 90, 60 HZ and device "OFF" state. RESULTS: Out of 40 patients, 38 patients showed a significant improvement in gait at a single frequency (best response frequency) which is different for each patient. The mean FOG score showed significant improvement at all stimulation frequencies when compared to OFF stimulation (P < 0.05). The mean number of steps was 18.9 at best response frequency and 21.48 at 130 Hz (P < 0.0001). Number of freezing episodes also were significantly less with best frequency when compared to 130 Hz stimulation (0.28 and 0.65 respectively, (P < 0.0001). The mean FOG score was 6.45 at best frequency and 9.48 at 130 Hz (P < 0.0001). Mean Dual tasking score was 3.53 at best frequency and 5.15 at 130 Hz (P < 0.0002). CONCLUSION: Optimization of frequency setting for each patient can improve gait and that each patient may have a different optimal frequency.

Systematic Development of Structured Semi-interactive Stroke Prevention Package for Secondary Stroke Prevention.

BACKGROUND: Lack of compliance to medication and uncontrolled risk factors are associated with increased risk of recurrent stroke and acute coronary syndrome in patients with recent stroke. Multimodal patient education may be a strategy to improve the compliance to medication and early adoption of nonpharmacological measures to reduce the vascular risk factor burden in patients with stroke. We thus aim to develop multilingual short messaging services (SMS), print, and audio-visual secondary stroke prevention patient education package. The efficacy of the package will be tested in a randomized control trial to prevent major cardiovascular and cerebrovascular events. METHODS: In the formative stage, intervention materials (SMS, video, and workbook) were developed. In the acceptability stage, the package was independently assessed and modified by the stakeholders involved in the stroke patient care and local language experts. The modified stroke prevention package was tested for implementation issues (implementation stage). RESULTS: Sixty-nine SMS, six videos, and workbook with 11 chapters with 15 activities were developed in English language with a mean ± SD SMOG index of 9.1 ± 0.4. A total of 355 stakeholders including patients (24.8%), caregivers (24.8%), doctors (10.4%), nurses (14.1%), local language experts (2.8%), physiotherapists (13.2%), and research coordinators (9.8%) participated in 10 acceptability stage meetings. The mean Patient Education Material Assessment Tool understandability score in all languages for SMS, video scripts, and workbook was 95.2 ± 2.6%, 95.2 ± 4.4%, and 95.3 ± 3.6%, respectively. The patients [n = 20, mean age of 70.3 ± 10.6 years and median interquartile range (IQR) baseline NIHSS 1 (0-3)] or the research coordinators (n = 2) noted no implementation issues at the end of 1 month. CONCLUSION: An implementable complex multilingual patient education material could be developed in a stepwise manner. The efficacy of the package to prevent major adverse cardiovascular events is being tested in the SPRINT INDIA study.

Impact of peroxynitrite modification on structure and immunogenicity of H2A histone.

Peroxynitrite is an extremely reactive entity and has in vivo existence. Its interaction with biomolecules may cause oxidation and nitration. In this study, commercially available H2A histone was exposed to peroxynitrite generated in vitro. The peroxynitrite-mediated structural changes in histone were studied by ultraviolet & fluorescence spectroscopy, high performance liquid chromatography, anilinonaphthalene-8-sulfonic acid binding and polyacrylamide gel electrophoresis. Analysis of results revealed that carbonyl, nitrotyrosine and dityrosine contents were significantly increased in peroxynitrite-modified H2A compared with native H2A. Rabbits challenged with peroxynitrite-modified H2A induced high titre antibodies. The immunogenicity of peroxynitrite-modified H2A was directly proportional to protein nitrotyrosine content and induced antibodies showed specificity for the immunogen and good cross-reaction with nitrated epitopes of other modified proteins. Formation of high molecular weight immune complex with retarded mobility further supports the specificity of induced anti-100 mum peroxynitrite-modified H2A antibodies for the immunogen. It may be concluded that induction of anti-H2A histone antibodies could be due to protection of peroxynitrite-modified histone from proteolytic breakdown and its subsequent recognition by immunoregulatory cells as foreign molecule.

Computational prediction of gene regulatory networks in plant growth and development.

Plants integrate a wide range of cellular, developmental, and environmental signals to regulate complex patterns of gene expression. Recent advances in genomic technologies enable differential gene expression analysis at a systems level, allowing for improved inference of the network of regulatory interactions between genes. These gene regulatory networks, or GRNs, are used to visualize the causal regulatory relationships between regulators and their downstream target genes. Accordingly, these GRNs can represent spatial, temporal, and/or environmental regulations and can identify functional genes. This review summarizes recent computational approaches applied to different types of gene expression data to infer GRNs in the context of plant growth and development. Three stages of GRN inference are described: first, data collection and analysis based on the dataset type; second, network inference application based on data availability and proposed hypotheses; and third, validation based on in silico, in vivo, and in planta methods. In addition, this review relates data collection strategies to biological questions, organizes inference algorithms based on statistical methods and data types, discusses experimental design considerations, and provides guidelines for GRN inference with an emphasis on the benefits of integrative approaches, especially when a priori information is limited. Finally, this review concludes that computational frameworks integrating large-scale heterogeneous datasets are needed for a more accurate (e.g. fewer false interactions), detailed (e.g. discrimination between direct versus indirect interactions), and comprehensive (e.g. genetic regulation under various conditions and spatial locations) inference of GRNs.