Facial morphology analysis of children with non-syndromic cleft lip and palate in a local population.

Objectives: To study the facial morphology in children with non-syndromic cleft lip and palate by applying numerical facial analysis on photographs for planning and evaluating treatment outcomes. Methods: This descriptive study was conducted from March 2020 to July 2020 in the Department of Oral Pathology, University of Health Sciences and Cleft Lip and Palate Hospital, Lahore Pakistan. A total of 104 patients of both genders with an age range from three months to thirteen years were included. Photographs of the participants were taken to measure facial anthropometrical landmarks including facial height, nose width, mouth width and inter canthal distance. The association between facial measurements with gender and phenotype and across age groups were computed keeping the confidence level at 95%. Results: Mean age of the children was 72.43±44.2 months with slight male predominance. Thirty-one percent presented with bilateral cleft lip and palate followed by unilateral cleft lip and plate. Total mean facial height, nose width and mouth width were found to be 143.46±21.52mm, 32.24±5.03mm and 33.71±4.38mm respectively. Intercanthal distance was measured to be 31.04±5.99mm. Statistically significant association was observed between gender and facial height, nose width, mouth width and Intercanthal distance. Conclusion: Facial anthropometric measures done on frontal photographs can be used to identify the facial landmarks in children with non-syndromic cleft lip and palate in low resource stings that may help surgeons in getting better aesthetic outcomes. These landmarks vary between ethnic groups therefore these should be specific to a particular race and ethnicity so as to ensure proper aesthetics and improved quality of life for the children of all nations.

Prevalence of Human Papilloma virus in potentially malignant oral disorders is a risk factor for development of early dysplasia-A cytological investigation.

Objective: The proposed study was planned to screen Human Papilloma Virus (HPV) status in potentially malignant oral disorders (PMOD) and correlated HPV positivity with cytological changes in oral smears. Methods: This descriptive cross-sectional study was conducted at University of Health Sciences Lahore, Pakistan from April 2020 to April 2021. Oral smears from N=162 patients with PMODs were taken by the Cytobrush and Manual Liquid Based Cytology was performed followed by p16 antibody detection on immunohistochemistry and HPV-DNA detection by conventional polymerase chain reaction (PCR). The cytological changes were categorized according to the updated Bethesda Classification system 2014. SPSS was used to analyze data and p-Value of <0.05 was considered as statistically significant. Results: Out of total N = 162 patients, the most prevalent lesion [39% (n=63)] was lichen planus. Fifty six percent (n=90) of the patients were habitual chewers and 43% (n=70) were smokers. Pap staining of oral smears revealed atypical squamous cells of undetermined significance (ASCUS) in 45% (n=69) cases and in 2 % (n=4) of the samples diagnosis of atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H) was made. A total of 37% cases showed HPV positivity by polymerase chain reaction (PCR) while positive p16 expression was observed in 24% of the cases. ASC-H and ASCUS category showed significant association with HPV positivity (p=0.003). Conclusion: Early detection of PMODs by adopting minimally invasive cytological techniques and screening for HPV infection in local population is pivotal to reduce the morbidity and mortality associated with the advanced disease and carcinoma.

Oral Squamous Cell Carcinoma Clinico-pathological features in relation to Tumor Stage; AJCC 2018 perspective.

Objective: To investigate the association between clinicopathological findings and tumor stage according to AJCC 2018 guidelines in patients suffering from Oral squamous cell carcinoma (OSCC). Methods: A descriptive study was conducted from January 2019 to January 2020 at King Edward Medical University and University of Health Sciences on a total of 49 patients enrolled after obtaining written informed consent. Clinical and radiographic findings were recorded. Pathological reporting was done using AJCC 2018 cancer staging guidelines. Association between clinicopathological features with tumor stage and grade was assessed using Chi-square and Kruskal-Wallis test. Result: Mean age of the patients was 46.1 ± 10.6 years. Most of the tumors were of well differentiated type (49%) and moderately differentiated (40.8%) with predominant clinical stage III in 42.9% & IV in 44.9 % and primary tumor stage pT2 28.6% & pT3 36.7%. Significant difference was seen for primary tumor stage in relation to age, gender, depth of invasion, primary site, and size of tumor (p < 0.01). For clinical stages, significant difference was observed in the age, gender, size of tumor, nodal metastasis, and anatomical tumor site (p < 0.01). Conclusion: Application of 8th Edition AJCC guidelines identifies the importance of the latest classification with strong association of latest stage criteria with age, gender, site of primary tumor, tumor thickness, depth of invasion, nodal metastasis and size of largest lymph node involved, and Level of Lymph node involved (level III & V) in a subset of patients from a developing country.

Rare Variant of Adult Rhabdomyosarcoma Presenting as a Palatal Swelling.

A 26-year-old male was referred to the Department of Oral and Maxillofacial Surgery of a tertiary care hospital in Lahore with chief complaint of painless swelling on the right palate of 40 days duration. Clinical differential diagnosis included squamous cell carcinoma, Ewing sarcoma, fibrosarcoma, neuroblastoma and rhabdomyosarcoma. Computed tomography scan revealed hypodense mass with necrotic changes. Histological examination of the excised tumor revealed malignant neoplasm arranged in fascicles and bundles comprising of spindle cells with pleomorphic, hyperchromatic nuclei and increased atypical mitosis. Immunohistochemical analysis showed negative staining with Cytokeratin, S100, CD34, Stat6, h-Caldesmon and EMA while the tumour cells were positive for desmin, myogenin, smooth muscle actin, CD-99 and MyoD1 thus confirming the diagnosis of spindle cell rhabdomyosarcoma.

Methicillin resistant coagulase negative staphylococcus: From colonizer to a pathogen.

The objective of our study was to determine the frequency of methicillin resistance in coagulase negative Staphylococcus (CoNS) and to determine its in-vitro antimicrobial susceptibility to various other routinely used antibiotics. It was a cross sectional study conducted at the department of Microbiology, Army Medical College, Rawalpindi, Pakistan from June 2011 to May 2012. The organisms were identified on the basis of colony morphology, Gram staining, catalase, DNAase and slide/tube coagulase tests. The organisms were considered to be methicillin resistant when the diameter of zone of inhibition was less than 25mm around 30µg cefoxitin disc. Antibiotic sensitivity was determined using the Modified Kirby-Bauer disc diffusion method. From a total of 337 CoNS, 201 were methicillin resistant and were included in the study. All were resistant to Penicillin, followed by Erythromycin (93•1%), Ciprofloxacin (77%), Co-trimoxazole (74•8%), Gentamicin (68•3%), Clindamycin (51•06%), Tetracycline (44•6%), Fusidic acid (40%), Rifampicin (39•5%), Chloramphenicol (19•3%), Linezolid (2%), Minocycline (1•1%), and Vancomycin (0%). More than half of CoNS were methicillin resistant. Vancomycin is the only drug to which all of the MRCoNS were sensitive, with more than 98% of the isolates being sensitive to Linezolid and Minocycline.

Coagulase negative staphylococci - a fast emerging threat.

OBJECTIVE: To determine the frequency of isolation of coagulase-negative staphylococci and their resistance to methicillin over a period of time. METHODS: The descriptive cross-sectional study was carried out at Army Medical College, Rawalpindi, from June 2009 to May 2012, and comprised clinical samples mostly from patients admitted to the intensive care unit. They were inoculated onto appropriate culture media depending upon the specimen. After 24-hour incubation at 35°C, coagulase-negative staphylococci were identified on the basis of colony morphology, gram staining, a positive catalase and a negative tube coagulase test.Methicillin resistance among the isolated staphylococci was determined using a 30µg Cefoxitin disc as per the Clinical and Laboratory Standards Institute protocol. Number of coagulase-negative staphylococci for each year and their methicillin resistance rates were calculated. A comparison was made with methicillin resistant staphylococcus aureus) isolated during the same period. RESULTS: Of the total 1331 specimens studies over three years, 581(43.65%) were coagulase-negative staphylococci. The rate of coagulase-negative staphylococci and methicillin resistance was higher each year; 110(26.6%) in May 2009-Jun 2010, 134(36.5%) in 2011, and 337(61%) in 2012. Methicillin resistance rates also increased from 25(22.7%) to 46(34.3%) and then to 201(59.6%) in 2012.Maximum isolated specimens came from blood 311(53.5%), followed by pus/swabs 204(35.1%). CONCLUSIONS: The frequency of isolation of coagulase-negative staphylococci and its methicillin resistance among hospitalised patients is on the rise.

Rem2 interacts with CaMKII at synapses and restricts long-term potentiation in hippocampus.

Synaptic plasticity, the process whereby neuronal connections are either strengthened or weakened in response to stereotyped forms of stimulation, is widely believed to represent the molecular mechanism that underlies learning and memory. The holoenzyme CaMKII plays a well-established and critical role in the induction of a variety of forms of synaptic plasticity such as long-term potentiation (LTP), long-term depression (LTD) and depotentiation. Previously, we identified the GTPase Rem2 as a potent, endogenous inhibitor of CaMKII. Here, we report that knock out of Rem2 enhances LTP at the Schaffer collateral to CA1 synapse in hippocampus, consistent with an inhibitory action of Rem2 on CaMKII in vivo. Further, re-expression of WT Rem2 rescues the enhanced LTP observed in slices obtained from Rem2 conditional knock out (cKO) mice, while expression of a mutant Rem2 construct that is unable to inhibit CaMKII in vitro fails to rescue increased LTP. In addition, we demonstrate that CaMKII and Rem2 interact in dendritic spines using a 2pFLIM-FRET approach. Taken together, our data lead us to propose that Rem2 serves as a brake on runaway synaptic potentiation via inhibition of CaMKII activity. Further, the enhanced LTP phenotype we observe in Rem2 cKO slices reveals a previously unknown role for Rem2 in the negative regulation of CaMKII function.

Neuroprotective potential of Mentha piperita extract prevents motor dysfunctions in mouse model of Parkinson's disease through anti-oxidant capacities.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Neurodegeneration of the substantia nigra (SN) and diminished release of dopamine are prominent causes of this progressive disease. The current study aims to evaluate the protective potential of ethanolic extract of Mentha piperita (EthMP) against rotenone-mediated PD features, dopaminergic neuronal degeneration, oxidative stress and neuronal survival in a mouse model. Swiss albino male mice were assigned to five groups: control (2.5% DMSO vehicle), PD (rotenone 2.5 mg/kg), EthMP and rotenone (200mg/kg and 2.5mg/kg, respectively), EthMP (200 mg/kg), and Sinemet, reference treatment containing levodopa and carbidopa (20 mg/kg and rotenone 2.5mg/kg). Behavioral tests for motor functional deficit analysis were performed. Anti-oxidant capacity was estimated using standard antioxidant markers. Histopathology of the mid-brain for neurodegeneration estimation was performed. HPLC based dopamine level analysis and modulation of gene expression using quantitative real-time polymerase chain reaction was performed for the selected genes. EthMP administration significantly prevented the rotenone-mediated motor dysfunctions compared to PD group as assessed through open field, beam walk, pole climb down, stepping, tail suspension, and stride length tests. EthMP administration modulated the lipid peroxidation (LPO), reduced glutathione (GSH), and superoxide dismutase (SOD) levels, as well as glutathione-s-transferase (GST) and catalase (CAT) activities in mouse brain. EthMP extract prevented neurodegeneration in the SN of mice and partially maintained dopamine levels. The expression of genes related to dopamine, anti-oxidant potential and synapses were modulated in M. piperita (MP) extract treated mice brains. Current data suggest therapeutic capacities of MP extract and neuroprotective capacities, possibly through antioxidant capacities. Therefore, it may have potential clinical applications for PD management.

In Vivo Study of Moringa oleifera Seed Extracts as Potential Sources of Neuroprotection against Rotenone-Induced Neurotoxicity.

Parkinson's disease (PD) is a leading neurodegenerative disorder affecting 1-3 percent of the elderly population. Oxidative stress is the primary factor for the neurodegeneration of Substantia Nigra (SN). The current study aims to assess the seed extracts of Moringa oleifera (MO) on rotenone-mediated motor function impairments in a PD mouse model. For this purpose, two different seed extracts of MO were prepared, including aqueous MO (AqMO) and ethanolic MO (EthMO). Male Swiss albino mice were grouped into five groups. Mice received 2.5 mg/kg rotenone for 21 consecutive days, and control mice received the vehicle. Extract-treated mice received 200 mg/kg AqMO and EthMO separately, orally and daily for 28 days. Sinemet-treated mice received 20 mg/kg, oral dose, as a positive group. The motor function performance was evaluated using standard neurobehavioral tests. The antioxidant potentials of MO seed extracts were estimated by lipid peroxidation (LPO), reduced glutathione (GSH), glutathione-s-transferase (GST) and catalase (CAT) activities in mice brain homogenates. The PD mice brain SN sections were investigated for neurodegeneration. MO seed extract-treated mice showed a significant reduction in motor dysfunction compared to rotenone-treated mice as assessed through the open field, beam walk, pole climb-down, tail suspension, stride length and stepping tests. Increased antioxidant capacities of the PD mice brains of MO extract-administered groups were observed compared to the control. A histological study showed reduced signs of neurodegeneration, vacuolation around multipolar cells and cytoplasmic shrinkage in MO extract-treated mice SN brain sections. Collectively, MO seed extracts protected the animals from locomotor deficits induced by rotenone, possibly through antioxidant means, and seem to have potential applications in neurodegenerative diseases.

In vitro efficacy of colistin against multi-drug resistant Pseudomonas aeruginosa by minimum inhibitory concentration.

Multi-drug resistant bacteria are an important cause of mortality and morbidity. In the management of various infections, timely detection and appropriate treatment, in accordance with the culture and sensitivity reports can help improve the treatment outcome. Colistin is a bactericidal antibiotic which is emerging as a reliable solution for treating infections with multi-drug resistant Gram negative bacilli. The aim of this study was to find out the in-vitro efficacy of colistin against multidrug resistant Pseudomonas aeruginosa isolates by minimum inhibitory concentration. This cross sectional, descriptive study was conducted in the Department of Microbiology, Army Medical College, National University of Sciences and Technology, Islamabad from February 2010 to January 2011. Antimicrobial sensitivity testing was done on Pseudomonas aeruginosa isolated from routine clinical specimens received and the strains which appeared resistant to at least one antimicrobial agent in three or more anti-pseudomonal antimicrobial categories were subjected to the Colistin Etest. The MIC endpoint of colistin was read, as per manufacturers instructions (AB Biodisk, Solna, Sweden). The isolates showing MIC of 2µg/ml or less were considered sensitive, those with 4-6µg/ml as intermediate and >µg/ml as resistant. MIC(50) and MIC(90) of colistin against MDR Pseudomonas aeruginosa was determined. A total of 52 MDR Pseudomonas aeruginosa strains were isolated during the period of the study. The highest percentage was isolated from urine (36%) followed by respiratory tract infections (18%) and pus specimens (20%). The highest percentage of these isolates was found to be susceptible to colistin followed by piperacillin-tazobactam and cefoperazone-sulbactam. A total of 36(69%) isolates were sensitive, 10(20%) were intermediate and 6(11%) were resistant to colistin by Kirby Bauer disc diffusion method. MIC(50) was found to be 1.0µg/ml while MIC(90) was 3.0µg/ml. Colistin is a reliable solution in cases of infections with MDR, XDR or PDR Pseudomonas aeruginosa.

Activity-dependent development of the body's touch receptors.

We report a role for activity in the development of the primary sensory neurons that detect touch. Genetic deletion of Piezo2, the principal mechanosensitive ion channel in somatosensory neurons, caused profound changes in the formation of mechanosensory end organ structures and altered somatosensory neuron central targeting. Single cell RNA sequencing of Piezo2 conditional mutants revealed changes in gene expression in the sensory neurons activated by light mechanical forces, whereas other neuronal classes were less affected. To further test the role of activity in mechanosensory end organ development, we genetically deleted the voltage-gated sodium channel Nav1.6 (Scn8a) in somatosensory neurons throughout development and found that Scn8a mutants also have disrupted somatosensory neuron morphologies and altered electrophysiological responses to mechanical stimuli. Together, these findings indicate that mechanically evoked neuronal activity acts early in life to shape the maturation of the mechanosensory end organs that underlie our sense of gentle touch.

Repair strategies for injured peripheral nerve: Review.

Compromised functional regains in about half of the patients following surgical nerve repair pose a serious socioeconomic burden to the society. Although surgical strategies such as end-to-end neurorrhaphy, nerve grafting and nerve transfer are widely applied in distal injuries leading to optimal recovery; however in proximal nerve defects functional outcomes remain unsatisfactory. Biomedical engineering approaches unite the efforts of the surgeons, engineers and biologists to develop regeneration facilitating structures such as extracellular matrix based supportive polymers and tubular nerve guidance channels. Such polymeric structures provide neurotrophic support from injured nerve stumps, retard the fibrous tissue infiltration and guide regenerating axons to appropriate targets. The development and application of nerve guidance conduits (NGCs) to treat nerve gap injuries offer clinically relevant and feasible solutions. Enhanced understanding of the nerve regeneration processes and advances in NGCs design, polymers and fabrication strategies have led to developing modern NGCs with superior regeneration-conducive capacities. Current review focuses on the advances in surgical and engineering approaches to treat peripheral nerve injuries. We suggest the incorporation of endothelial cell growth promoting cues and factors into the NGC interior for its possible enhancement effects on the axonal regeneration process that may result in substantial functional outcomes.

Parkinson's disease: Mechanisms, translational models and management strategies.

Parkinson's disease is a progressive neurodegenerative disorder. The classical motor symptoms include resting tremors, bradykinesia, rigidity and postural instability and are accompanied by the loss of dopaminergic neurons and Lewy pathology. Diminished neurotransmitter level, oxidative stress, mitochondrial dysfunction and perturbed protein homeostasis over time worsen the disease manifestations in elderly people. Current management strategies aim to provide symptomatic relief and to slow down the disease progression. However, no pharmacological breakthrough has been made to protect dopaminergic neurons and associated motor circuitry components. Deep brain stimulation, stem cells-derived dopaminergic neurons transplantation, gene editing and gene transfer remain promising approaches for the potential management of neurodegenerative disease. Toxin or genetically induced rodent models replicating Parkinson's disease pathology are of high predictive value for translational research. This review addresses the current understanding, management strategies and the Parkinson's disease models for translational research. Preclinical research may provide powerful tools to quest the potential therapeutic and neuroprotective compounds for dopaminergic neurons and hence possible cure for the Parkinson's disease.

In vitro Efficacy of Meropenem, Colistin and Tigecycline Against the Extended Spectrum Beta-Lactamase Producing Gram Negative Bacilli.

OBJECTIVE: To compare the in vitro efficacy of meropenem, colistin and tigecycline against extended spectrum Betalactamase producing Gram negative bacilli by minimal inhibitory concentration. STUDY DESIGN: Cross-sectional descriptive study. PLACE AND DURATION OF STUDY: Department of Microbiology, Army Medical College, National University of Sciences and Technology, Rawalpindi, from June to December 2010. METHODOLOGY: Routine clinical specimens were subjected to standard microbiological procedures and the isolates were identified to species level. Extended spectrum ß-lactamase producing Gram negative bacilli were detected by Jarlier disc synergy method and confirmed by ceftazidime and ceftazidime-clavulanate Etest. Minimum Inhibitory Concentration (MIC(90)) of meropenem, colistin and tigecycline was determined by Etest (AB BIOMERIUX) and the results were interpreted according to the manufacturer's instructions and Clinical and Laboratory Standards Institute guidelines and Food and Drug Authority recommendations. Results were analyzed by using Statistical Package for the Social Sciences version 20. RESULTS: A total of 52 non-duplicate extended spectrum Beta-lactamase-producing Gram negative bacilli were included in the study. The MIC(90) of tigecycline (0.75 µg/ml) was lowest as compared to the meropenem (2 µg/ml) and colistin (3 µg/ml). CONCLUSION: Tigecycline is superior in efficacy against the extended spectrum Beta-lactamase producing Gram negative bacilli as compared to colistin and meropenem.

Frequency and antibiogram of vancomycin resistant enterococcus in a tertiary care hospital.

OBJECTIVE: To determine the frequency of Vancomycin Resistant Enterococcus (VRE) in a tertiary care hospital of Rawalpindi, Pakistan. STUDY DESIGN: Observational, cross-sectional study. PLACE AND DURATION OF STUDY: Department of Microbiology, Army Medical College, Rawalpindi, from May 2011 to May 2012. METHODOLOGY: Vancomycin resistant Enterococcus isolated from the clinical specimens including blood, pus, double lumen tip, ascitic fluid, tracheal aspirate, non-directed bronchial lavage (NBL), cerebrospinal fluid (CSF), high vaginal swab (HVS) and catheter tips were cultured on blood agar and MacConkey agar, while the urine samples were grown on cystine lactose electrolyte deficient agar. Later the antimicrobial susceptibility testing of the isolates was carried out using the modified Kirby-Bauer disc diffusion method on Mueller Hinton agar. RESULTS: A total of 190 enterococci were isolated. Of these, 22 (11.57%) were found to be resistant to vancomycin. The antimicrobial sensitivity pattern revealed maximum resistance against ampicillin (86.36%) followed by erythromycin (81.81%) and gentamicin (68.18%) while all the isolates were 100% susceptible to chloramphenicol and linezolid. CONCLUSION: The frequency of VRE was 11.57% with the highest susceptibility to linezolid and chloramphenicol.

Frequency and antibiogram of multi-drug resistant Pseudomonas aeruginosa.

OBJECTIVE: To find out the frequency and susceptibility pattern of multi-drug resistant (MDR) Pseudomonas aeruginosa in clinical specimens. STUDY DESIGN: Cross-sectional observational study. PLACE AND DURATION OF STUDY: Department of Microbiology, Army Medical College, National University of Sciences and Technology (NUST), Rawalpindi, from January to September 2010. METHODOLOGY: Routine clinical specimens were subjected to standard microbiological procedures and the isolates were identified to the species level. The antibiotics susceptibility was determined by Kirby Bauer Disc diffusion method and the results were interpreted according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: The frequency of MDR Pseudomonas aeruginosa among all the Pseudomonas aeruginosa strains isolated was found to be 22.7%. These isolates were most sensitive to Colistin followed by Piperacillin-Tazobactam and Cefoperazone-Sulbactum. CONCLUSION: Increasing fequency of infections due to MDR Pseudomonas aeruginosa is an emerging threat in our set up which an be prevented by prescribing antibiotics judiciously and by adopting proper disinfection measures.