Yellow scorpion (Buthus sinidicus) venom peptides induce mitochondrial-mediated apoptosis in cervical, prostate and brain tumor cell lines.

Scorpion venoms are known to contain over 100,000 biologically active constituents. However, only a few of them have been studied. The major constituents of venom are proteins and peptides, which exhibit various biological and pharmacological properties, including anticancer activities. In the current study, the venom of yellow scorpions (Buthus sindicus) found in Sindh, Pakistan, was extracted and evaluated for its anti-cancer and anti-inflammatory activities. The crude venom showed a dose dependent inhibition of phagocyte oxidative burst from human whole blood cells (28.3% inhibition at highest tested concentration of 300 µg/mL). In-vitro cytotoxicity of crude venom was evaluated against human prostrate (PC3), cervical (HeLa) and neuroblastoma (U87-MG) cell lines, along with cytotoxicity against normal human fibroblast (BJ) cells. Crude venom was cytotoxic to all cell lines, with prominent inhibitory effect on PC3 cells. Crude venom was fractionated through RP-UPLC, resulted in fifteen fractions, followed by evaluation of their anticancer potential. Among all, the fraction I significantly (P < 0.001) reduced the cell viability of all three cancer cell lines, and exhibited insignificant cytotoxicity against normal cell line. Furthermore, the apoptotic cell death pathway was evaluated for crude venom, and fraction I, in most sensitive cell line PC3, by using flow-cytometry analysis. Both crude venom and its fraction I caused a mitochondrial-mediated apoptosis in prostate cancer cells (PC3). To the best of our knowledge, this is the first report of the anticancer and anti-inflammatory activity of venom of Pakistani yellow scorpions. Results indicate their therapeutic potential, and a case for further purification and validation studies.

Epithelial Myoepithelial Carcinoma Masquerading as Simple Parotid Cyst in a Middle Aged Male.

Epithelial-Myoepithelial Carcinoma (EMC) is a very rarely seen biphasic tumour typically seen in older females and constitutes 0.5-1% of all salivary gland neoplasms. The parotid gland is most often involved and occasionally there may be involvement of submandibular and minor salivary glands. Clinical picture often reveals benign nature of the disease. Computed tomography (CT) and magnetic resonance appearances are non-specific and the cytological diagnosis may be challenging, thus more accurate diagnosis can only be made by histological and immunohistochemical study. There is no consensus regarding the optimal treatment of this neoplasm, largely due to its rarity. Wide surgical excision with a clear margin is the treatment of choice because of the tumour's tendency to infiltrate locally. Adjuvant radiotherapy is often required in cases of large primary tumours and positive surgical margins. The tumour may commonly recur locally after resection in 30-50% of cases. We herein present an unusual case of a 46-year-old male who presented with cystic swelling of left parotid gland and diagnosed as EMC on histopathology and immunohistochemical examination. The patient was treated with surgical resection followed by post-operative radiotherapy.

Ears with Cholesteatoma: Outcomes of Canal Wall Up and Down Tympano-Mastoidectomies-A Comparative Prospective Study.

This prospective study has been carried out to observe the outcomes of canal wall up (CWU) and canal wall down (CWD) Tympano-mastoidectomies in ears with cholesteatoma. Outcomes of the procedures have been done in terms of recurrence of cholesteatoma, complications, graft uptake rates and post-operative hearing gain. This study was carried out in the Department of Otorhinolaryngology of a reputed tertiary teaching hospital of North India from January 2016 to June 2020, with a mean follow-up of 32 months. The study included 100 patients of otitis media with cholesteatoma. In Canal Wall Up Tympano-mastoidectomy (CWUT) group, the number of males and females were 22 each. On the other hand, 36 males and 20 females underwent Canal Wall Down Tympano-mastoidectomy (CWDT). Each surgery was done as a single-staged and at the end of the surgical procedure angled oto-endoscopes were used for ensuring complete removal of the disease. Though there is no statistically significant difference in recurrence of cholesteatoma and complications rate in CWU and CWD Tympano-mastoidectomy techniques, but CWUT is superior to CWDT in terms of better graft uptake (p = 0.0156), and better average audiological gain (8.56 ± 0.93 dB) with p value = 0.0315. A diligent post-operative follow-up is must for assessing the outcomes of different types of mastoidectomies. This study shows no statistical difference in the disease recurrence and complication rates between Canal Wall Up and Down Tympano-mastoidectomies, though the anatomical changes and creation of the mastoid cavity in canal wall down procedure may affect the graft uptake and post-operative hearing gain. Use of Oto-endoscopes in cholesteatoma surgery helps in improving the outcomes of both techniques and thus recommended if the facility for the same is available.

Bacteriological and Antibiotic Sensitivity Profile of Cholesteatomatous Otitis Media in Pediatric and Adult Population: Prevailing Scenario in Northern India.

The bacteriological and antimicrobial sensitivity profile of chronic otitis media (COM) varies from region to region and from time to time and may vary among different age group as well. It was against this backdrop of the changing bacteriological profile and sensitivity pattern together with the paucity of categorically separated data of pediatric and adult population, that the present study was undertaken. A total of 193 patients of clinical diagnosis of cholesteatomatous COM with ear discharge and positive culture results were included in the study. Pus sample was collected under aseptic conditions and cultured on solid media and broth. Isolates were identified via standard biochemical tests and sensitivity patterns analysed. Chi square (χ2) test was used to analyse the significance. Pseudomonas was the most common isolate in both the pediatric (37.80%) and adult (51.46%) population. Methicillin sensitive staph aureus (MSSA) was found exclusively in pediatric population (p = 0.003).Piperacillin-Tazobactam combination was the single most effective drug regimen overall. 75% of pseudomonas isolates in pediatric and 87.5% in adults were sensitive to this regimen in vitro. Amikacin was the next most effective drug with 56.69% sensitivity in pediatric and 64.08% sensitivity in adult population. The present study finds piperacillin-tazobactam as the most effective therapy and pseudomonas as the most common isolate in the study population.In order to address the varying and changing bacteriological and sensitivity profile of chronic otitis media occurring among different geographical regions and also within a region over time, the authors recommend its periodic evaluation.

Microbiological Assessment of Chronic Otitis Media: Aerobic Culture Isolates and Their Antimicrobial Susceptibility Patterns.

As there are changing trends in the microbiology of chronic otitis media, this study was carried out to look for the current aerobic microbes and their antimicrobial susceptibilities in patients of chronic otitis media from north Indian region. A total of 322 patients who met the inclusion criteria were studied and aerobic ear swab culture was done under aseptic conditions. Gram staining was performed and antibiotic susceptibility testing was done using Kirby-Bauer disc diffusion method on Mueller-Hinton Agar. A total of 341 culture positive results were obtained from 322 patients. The culture results revealed 10 different aerobic microbes. Gram-positive floras were seen in 152 (44.57%), and Gram-negative in 189(55.43%) isolates. Staphylococcus aureus was the most common isolate present in 131 samples (38.41%), followed by pseudomonas aeruginosa in 101 (29.62%) and proteus in 36 (10.56%). In overall susceptibility of antibiotics against Gram-positive culture isolates, Vancomycin was most effective (97.37%). For Gram-negative microbes, Piperacillin-Tazobactum combination was most effective with overall susceptibility of 79.37% susceptibility. Microbiological assessment of Chronic Otitis Media should be carried out in an area on regular intervals because of the changing patterns of bacteriology and their antimicrobial susceptibilities.

Combating effects of Azadirachta indica leaves extract on biochemical and neuropsychological decline observed in diabetes.

Diabetes is a group of metabolic disorder effecting health of wide number of population and cause neuropsychological decline. In the present study, effect of AI leaves extract on neuropsychological behaviors was observed in diabetic rat's model. Rats were divided into 4 groups as control (saline treated healthy rats), positive control (pioglitazone treated diabetic rats), diabetic control (untreated diabetic rats) and AI leaves extract treated diabetic rats. Diabetes was induced by giving 35% fructose for 6 weeks and a single dose of Streptozotocin (40 mg/kg). After 3 weeks of treatment behavioral and biochemical analysis were done. Behavioral results revealed that induction of type 2 diabetes produced anxiety, depression, decreased motor activity and impaired recognition memory in rats. Treatment with AI leaves extract in diabetic rats significantly decreased anxiety, depression, increased motor activity, enhanced recognition memory. Biochemical investigation revealed that AI leaves extract treat diabetes via improving the levels of fasting insulin and HbA1c and a significant decrease in CK and SGPT levels were observed in AI leaves treated diabetic rats. So, AI besides treating diabetes, helps in lowering the risk of co-occurring diabetic diseases and found effective in lowering neuropsychological decline observed in type 2 diabetes.

Tryptophan lessens reserpine induced anxiety, depression and memory impairment by modulating oxidative stress and serotonergic activity.

Reserpine (Res)-induced depletion of monoamines and altered neurotransmission and produces oxidative stress. Tryptophan (TRP) regulated the serotonin neurotransmission. Because systemically injected Res induced behavioral deficits and oxidative stress, while, dietary components prevented these adverse effects, we used TRP a pharmacological tool to prevent Res- induced changes in behavior, memory impairments, oxidative stress and regulation of serotonin neurotransmission in rats. Anxiolytic, antidepressant, cognitive functions, lipid peroxidation, antioxidant enzymes serotonin metabolism were studied in Res and vehicle treated animals following administration of 50 and 100 mg/ml/kg of tryptophan. Following administration of TRP [50 and 100mg/ml/kg], Res induced anxiety-and/or depression like behaviors normalized. Res-induced impaired cognitive function and increased acetylcholinesterase activity also improved following administration of TRP at both doses. Res induced increased brains' malondialdehyde (MDA) and decreased antioxidant enzymes activity also normalized by TRP. Res-induced decreased 5-HT metabolism also regulated by administration of TRP at both doses. In conclusion it can be recommended that administration/supplementation of TRP in daily life can aid in battling the anxiety, depression, modulating serotonergic activity and oxidative stress. Study also exhibits the anti-acetylcholinesterase role of TRP which may be possible reason for improved cognition following stress situation.

Biosynthesis of silver nanoparticles from Mukia maderaspatana (L) and their biological activities.

Nanotechnology is a field of science that consists of atoms, molecules and supramolecular molecules that create nanoparticles ranging in size from 1-100nm. Silver nanoparticles are widely used that are considered as effective antimicrobial agents. In this paper, the antioxidant activity of biosynthesized SNPs were analyzed by the DPPPH activity, hydrogen peroxide activity, hydroxyl RSA, TAC, TFC; their results confirmed that the phenolic compounds of this plant peels extracts enhanced the antioxidant and antiglycation activity with respect to silver nanoparticles. Biosynthesized nanoparticles of this plant extracts also showed strong zone of inhibition against the different Xanthomas, Pseudomonas and E. coli. This study concluded that biosynthesized nanoparticles of Mukia maderaspatna (M.M) plant peels extracts have the great biological activities i.e. antiglycation, antioxidant and antibacterial. More research is needed to know the exact dose rate and to compare the different dose combination of the plant with the strong antibiotic agents against these bacteria.

Anti-leucine-rich-glioma-inactivated 1 Limbic Encephalitis: An Underrecognised Disease.

Autoimmune limbic encephalitis is a rare autoimmune disease characterised by inflammation of the limbic system of the brain. The disease runs a sub-acute course with cognitive impairment, memory loss and seizures. These patients have been underdiagnosed in Pakistan. Here, we present a case of a middle-aged male, who presented to our Department after having multiple visits to different psychiatrists for his symptoms. The patient had been put on multiple psychiatric and antiepileptic medications, but his condition gradually declined. At our Department, he was thoroughly assessed and then diagnosed as limbic encephalitis on the basis of the typical history, positive anti-leucine-rich-glioma-inactivated 1 (LGI1) antibodies and MRI findings. The patient responded to plasmapheresis and immune modulating therapy and is being followed up. Emphasis is made on early diagnosis; and earlier treatment of such cases, as it holds a substantial importance in management and makes a difference in future outcome. Key Words: Autoimmune limbic encephalitis, Voltage-gated potassium channels, Cognitive dysfunction.

Zygomatico-Coronoid Pseudoarthrosis Due to Osteochandroma of Coronoid Process: A Rare Entity.

INTRODUCTION: Osteochondroma of the coronoid process also known as Jacob's disease, has rarely been reported in the literature and it posses a challenge as diagnosis may be overlooked in favour of other causes of limited mouth opening. CASE REPORT: This is a case report of an adult male patient who presented with restricted mouth opening in whom radiological imaging, especially 3D computed tomography, played a role in establishing the diagnosis of Jacob's disease. CONCLUSION: An osteochondroma of the coronoid process of the mandible (Jacob's disease) is a rare cause of restricted mouth opening and its diagnosis can be overlooked in favour of TMJ ankylosis. The CT scan plays an important role in diagnosis and in planning for surgery.

Application of stacking hybrid machine learning algorithms in delineating multi-type flooding in Bangladesh.

Floods are among the most devastating natural hazards in Bangladesh. The country experiences multi-type floods (i.e., fluvial, flash, pluvial, and surge floods) every year. However, areas prone to multi-type floods have not yet been assessed on a national scale. Here, we used locally weighted linear regression (LWLR), random subspace (RSS), reduced error pruning tree (REPTree), random forest (RF), and M5P model tree algorithms in a hybrid ensemble to assess multi-type flood probabilities at a national scale in Bangladesh. We used historical flood data (1988-2020), remote sensing images (e.g., MODIS, Landsat 5-8, and Sentinel-1), and topography, hydrogeology, and environmental datasets to train and validate the proposed algorithms. According to the results, the stacking ensemble machine learning LWLR-RF algorithm performed better than the other algorithms in predicting flood probabilities, with R2 = 0.967-0.999, MAE = 0.022-0.117, RMSE = 0.029-0.148, RAE = 4.48-23.38%, and RRSE = 5.8829.69% for the training and testing datasets. Furthermore, true skill statistics (TSS: 0.929-0.967), corrected classified instances (CCI: 96.45-98.35), area under the curve (AUC: 0.983-0.997), and Gini coefficients (0.966-0.994) were computed to validate the constructed (LWLR-RF) multi-type flood probability maps. The maps constructed via the LWLR-RF algorithm revealed that the proportions of different categories of flooding areas in Bangladesh are fluvial flooding 1.50%, 5.71%, 12.66%, and 13.77% of the total land area; flash floods of 4.16%, 8.90%, 11.11%, and 5.07%; pluvial flooding: 5.72%, 3.25%, 5.07%, and 0.90%; and surge flooding, 1.69%, 1.04%, 0.52%, and 8.64% of the total land area, respectively. These percentages represent low, medium, high, and very high probabilities of flooding. The findings can guide future flood risk management and sustainable land-use planning in the study area.

Simultaneous modelling of coagulant recovery and reuse by response surface methodology.

Surface water from rivers, lakes, reservoirs etc. needs to be treated prior to municipal supplies. The treatment scheme includes coagulation, flocculation, sedimentation, filtration and finally disinfection process. Huge volume of sludge or waste is generated during the coagulation-flocculation. Disposal of the sludge so generated in the treatment plants require careful consideration for managing it sustainably and in an environment friendly manner. Constructive utilization of the inevitable waste may help in finding a sustainable solution to sludge disposal problems. Presently, response surface methodology (RSM) with central composite design (CCD) has been applied to simultaneously model coagulant recovery as well as reuse parameters. In order to simplify the process and increase the applicability, the effect of three significant variables, acid dose, sludge ratio, and recovered coagulant dose are studied. A second order regression model has been developed which gave the optimum combination of acid dose of 30 ml/L, sludge ratio of 1% and recovered coagulant dose of 12 ml/L for maximum turbidity removal. The predicted value of turbidity removal is 95.4%. In the confirmatory experiments, the turbidity removal value was observed to be about 96.2%, which is in good agreement with the predicted value. In addition to turbidity removal, it also helps to effectively remove other impurities from the raw water for it to meet the standards prescribed for potable supply. Thus, the regenerated alum or recovered coagulant has the potential to substitute the conventional coagulants, fully or partially at water treatment plants.

The nexus of tourism, renewable energy, income, and environmental quality: an empirical analysis of Pakistan.

In the current study, we investigate the dynamic association of tourism, renewable energy, income, foreign direct investment (FDI), and carbon dioxide (CO2e) for Pakistan over 1990-2017. We established four plausible hypotheses and verified by employing the autoregressive distributed lags model and Granger causality based on vector error correction model (VECM). Considering the cointegration relationship between the variables, the outcomes of autoregressive distributed lags suggested that tourism increases economic growth, and economic growth induces tourism in the long-run, thus confirming tourism-led development, and growth-led tourism hypothesis; similarly, the tourism generates CO2e emissions, which supported the tourism-led emission hypothesis. The role of renewable energy consumption found to be a significant moderator, thus helping to enrich tourism, accelerating economic growth, and combating CO2e in the country. VECM causal results indicated the significant bidirectional causal linkages between tourism and economic growth-another causality found between tourism and CO2e. There is one-way causality from FDI and renewable energy towards income simultaneously. Overall, the designers of policies will find this study useful for policymaking at government levels for smooth economic growth, investment, and sustainable tourism sector.

The Spectrum of Movement Disorders in Anti-N-Methyl-D-Aspartate Receptor (NMDAR) Encephalitis Both in Children and Adults: An Experience From a Single Tertiary Care Center.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a form of autoimmune encephalitis. The characteristic clinical features include seizure, psychosis-like symptoms, abnormal movements, and autonomic disturbances. Patients with anti-NMDAR encephalitis can present with various types of movement disorders. Typically, the movement disorders start following intervals of psychiatric and prodromal manifestations in young adults; however, in children, these might be an early presentation of anti-NMDAR encephalitis. The disease is under-recognized and underdiagnosed in Pakistan. Early recognition of the disease is important to commence timely treatment leading to a better prognosis. Here we present a collection of anti-NMDAR encephalitis patients, specifically focussing on the different types of movement disorders and the differences in clinical manifestations between children and adults.

Exposure to noise augments behavioral deficits in mice: Protective effect of banana peel extract.

The study is aimed to evaluate the protective impact of banana peel extract (BPE) following noise induce behavioral deficits in male mice. Animals were separated into two groups (control and test, 12 in each). Control mice were given drinking water, at the same time test group was given BPE (400 mg/kg; oral administration). Animals have received their respective treatment for 14 days. Mice were subdivided (n=6) into unstressed and stressed groups on day 15. Noise stress was given to the respective group for 4-h. Behavioral activities were monitored 24-h after the 4-h noise stress. Forced-swim-test, Elevated-plus-maze and light-dark-activity-box tests were performed for depression/anxiety-like behaviors respectively. Morris-water-maze assessment was used for memory. After behavioral tests animals were sacrificed and brain was detached for biochemical estimations and histopathological studies. In the present study, BPE produced anxiolytic and antidepressant-like effects and enhanced memory. Activity of antioxidant enzymes increased while levels of AChE and MDA decreased in BPE treated animals. Histopathological alterations induced by noise stress were also normalized by BPE. It is concluded that supplementation/administration of banana peel has preventive effects against anxiety, depression and memory impairment via its strong antioxidant potential following NS.

Klippel-Feil Syndrome With Auxiliary Anterior Cervical Meningomyelocele and Thoracic Syringomyelia: A Case Report.

STUDY DESIGN: Case report. OBJECTIVE: Since this is the first ever case of a male patient with Klippel-Feil syndrome (KFS) with anterior cervical meningomyelocele and syringomyelia. All four previously reported cases were female patients. This makes this case unique. SUMMARY OF BACKGROUND DATA: KFS with auxiliary anterior cervical meningomyelocele is a rare entity. To the best of our knowledge so far only four cases are reported. METHODS: A 22-year-old male patient was presented to neurology outpatient department with 2-year history of left hand paresthesia and progressive weakness. The diagnostic evaluation showed KFS with auxiliary anterior cervical meningomyelocele and thoracic syringomyelia. RESULTS: Patient was sent to neurosurgery department for intervention. After discussing the possible risks and complications of intervention he opted for conservative therapy and declined the surgery. CONCLUSION: The paucity of data is the key reason for any recommended protocol for management of such patients but the available literature recommends neurosurgical intervention in symptomatic patients. LEVEL OF EVIDENCE: 5.

Mitomycin-C in Post-endoscopic Septoplasty Synechiae: Does it Really Helps?

Endoscopic septoplasty has advantage of magnified image and access to posterior part of the septum. Synechiae formation is a common complication of this procedure. The incidence of adhesions rises particularly in cases of submucosal flap tears which is sometimes unavoidable during spurectomy. Various procedures like septal splints, nasal packings have been tried to reduce the incidence of adhesions. Recently mitomycin-C is being tried to decrease post operative adhesions after Functional Endoscopic Sinus Surgery, endoscopic Dacrocystorhinostomy, with varying degree of success. Mitomycin-C has got anti fibroblastic activity, which inhibits the fibroblasts without hampering epithelization. Eighty (80) Patients undergoing septoplasty and spurectomy were observed for any submucosal flap tear, and those developing flap tear were included in the study. The patients were divided into 2 groups of 40 each. In group-1 topical mitomycin (0.4 mg/ml) was applied at the raw area for 5 min, similarly normal saline was applied in group-2 (control).The aim of study was to evaluate the role of mitomycin-C in preventing post operative adhesions in Endoscopic septoplasty. Adhesion rate was calculated at 1 month, and compared using Chi square test. P value < 0.05 was considered significant. The adhesion rate at 1 month was 17.5% in group-1 and 45% in group-2 (P = 0.008). Incidence of adhesion decreased significantly in mitomycin-C treated group. Mitomycin-C can routinely be used in septoplasty to prevent post op adhesions, particularly in cases of submucosal flap tears/concurrent turbinate reduction procedures.

Sequential Optic Neuritis: A Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune relapsing demyelinating disorder which often leads to severe disability typically targeting spinal cord, optic nerves, and brainstem. Around 75% of NMOSD patients have serum immunoglobulin-G (IgG) autoantibodies to the aquaporin-4 channel (AQP4-IgG). AQP4-IgG antibodies have a central role in new diagnostic criteria of NMOSD. These antibodies have a critical role in long-term management after the first attack. The prevalence of this disorder is lower than multiple sclerosis in European countries. However, NMO makes a substantial proportion of the demyelinating diseases of the central nervous system in countries like Pakistan, where it can be mistaken for multiple sclerosis. Accurate diagnosis is essential as some of the drugs for multiple sclerosis can potentially worsen NMOSD. We present a case of sequential optic neuritis with positive aquaporin 4 antibodies. We have discussed the history, examination findings, diagnostic workups, and treatment of the patient.

Dyke-Davidoff-Masson Syndrome: An Unusual Cause of Status Epilepticus and Refractory Seizures.

Dyke-Davidoff-Masson Syndrome (DDMS) is a rare neurological condition characterised by drug-resistance seizures, hemiparesis, mental retardation, facial asymmetry, and intellectual disabilities. On brain imaging, the disease is characterised by cerebral hemiatrophy with ipsilateral calvarial thickening and hyperpneumotisation of paranasal sinuses or mastoid air cells. Although more common in men and on the left side of the brain, the disease can affect both genders and cerebral hemispheres. It mainly presents in childhood. The adult presentation is unusual but has been reported in medical literature. Most of the patients need more than one antiepileptic agent for optimal control of seizures. Hemispherectomy is reserved for patients who have drug-resistant and disabling seizures. The good prognostic factors are disease onset before age of two and better seizure control. We report two cases of DDMS occurring in teenage boys who presented with status epilepticus. The clinical histories, radiological findings, and treatment of both patients are discussed below.