Story of the solitary subependymal giant cell astrocytoma: A case report and literature review.

Subependymal giant cell astrocytoma (SEGA) is the characteristic benign, slow-growing brain tumor seen in tuberous sclerosis (TS). There are several case reports of a diagnosis of SEGA in patients with no clinical or radiological diagnosis of TS. However, there is limited literature describing the tumor genetics in such cases. We report a case of a 17-year-old girl who was diagnosed with SEGA bearing the TSC2 mutation, while testing negative for TSC mutations on germline testing. We also did a literature review of studies that reported the genetics behind solitary SEGAs. Genetic testing of both the tumor itself and germline genetic testing can provide valuable information with clinical implications, for example, the basis for the need of close surveillance in TS patients.

Development of antibiotic resistance in the ocular Pseudomonas aeruginosa clone ST308 over twenty years.

Corneal infection caused by a bacteria Pseudomonas aeruginosa is common cause of ocular morbidity. Increasing antibiotic resistance by ocular P. aeruginosa is an emerging concern. In this study the resistome of ocular isolates of Pseudomonas aeruginosa clone ST308 isolated in India in 1997 (PA31, PA32, PA33, PA35 and PA37) and 2018 (PA198 and PA219) were investigated. All the isolates of ST308 had >95% nucleotide similarity. The isolates from 2018 had larger genomes, coding sequences, accessory and pan genes compared to the older isolates from 1997. The 2018 isolate PA219 was resistant to all antibiotics except polymyxin B, while the 2018 isolate PA198 was resistant to ciprofloxacin, levofloxacin, gentamicin and tobramycin. Among the isolates from 1997, five were resistant to gentamicin, tobramycin and ciprofloxacin, four were resistant to levofloxacin while two were resistant to polymyxin B. Twenty-four acquired resistance genes were present in the 2018 isolates compared to 11 in the historical isolates. All isolates contained genes encoding for aminoglycoside (aph(6)-Id, aph(3')-lIb, aph(3″)-Ib), beta-lactam (blaPAO), tetracycline (tet(G)), fosfomycin (fosA), chloramphenicol (catB7), sulphonamide (sul1), quaternary ammonium (qacEdelta1) and fluoroquinolone (crpP) resistance. Isolate PA198 possessed aph(3')-VI, rmtD2, qnrVC1, blaOXA-488, blaPME-1, while PA219 possessed aadA1, rmtB, qnrVC1, aac(6')-Ib-cr, blaTEM-1B, blaVIM-2, blaPAO-1, mph(E), mph(A), msr(E). In both recent isolates qnrVC1 was present in Tn3 transposon. In 219 blaTEM-1 was carried on a transposon and blaOXA-10 on a class 1 integron. There were no notable differences in the number of single nucleotide polymorphisms, but recent isolates carried more insertions and deletions in their genes. These findings suggest that genomes of P. aeruginosa ocular clonal strains with >95% nucleotide identity isolated twenty years apart had changed over time with the acquisition of resistance genes. The pattern of gene mutations also varied with more insertions and deletions in their chromosomal genes which confer resistance to antibiotics.

Is Pakistan prepared for the COVID-19 epidemic? A questionnaire-based survey.

COVID-19 is a pandemic that began in China in December 2019. World health organization (WHO) has expressed fears that Pakistan might emerge as the next epicenter of this pandemic. We hypothesize that at present the Pakistani masses are not prepared to face any threat of a looming epidemic. The main aim of this study was to evaluate the basic knowledge of educational and health care workers (HCWs) regarding COVID-19, its control, and prevention. Knowledge about origin, symptoms, and spread of viral infection was assessed. In this cross-sectional survey, a self-designed questionnaire was distributed among 302 HCWs including physicians (10.9%), nurses (1.32%), lab staff (1.65%), and academic individuals including faculty and students (86.42%) of different organizations. Results were analyzed using the χ2 test. Obtained results validate our null hypothesis that Pakistani masses are not well aware of the COVID-19 and strategies for the prevention and control of infection. The study concluded that individuals belonging to the front-line workers and high literacy groups are not prepared for the alarming situation in the country. Effectual implementation of infection control programs should be practiced, and it depends on awareness, training, and cooperation of individuals.

Aspartate aminotransferase to platelet ratio and fibrosis-4 as biomarkers in biopsy-validated pediatric cystic fibrosis liver disease.

UNLABELLED: Up to 10% of cystic fibrosis (CF) children develop cirrhosis by the first decade. We evaluated the utility of two simple biomarkers, aspartate aminotransferase to platelet ratio index (APRI) and FIB-4, in predicting degree of fibrosis in pediatric CF liver disease (CFLD) validated by liver biopsy. In this retrospective, cross-sectional study, 67 children with CFLD had dual-pass liver biopsies and 104 age- and sex-matched CF children without liver disease (CFnoLD) had serum to calculate APRI and FIB-4 collected at enrollment. CFLD was defined as having two of the following: (1) hepatomegaly±splenomegaly; (2)>6 months elevation of ALT (>1.5× upper limit of normal ULN); or (3) abnormal liver ultrasound findings. Biopsies were staged according to Metavir classification by two blinded pathologists. Receiver operating characteristic (ROC) analysis and continuation ratio logistic regression were performed to assess the predictability of these biomarkers to distinguish CFLD from CFnoLD and determine fibrosis stage-specific cut-off values. The AUC for APRI was better than FIB-4 (0.75 vs. 0.60; P=0.005) for predicting CFLD and severe CFLD (F3-F4) (0.81). An APRI score>0.264 demonstrated a sensitivity (95% confidence interval [CI]) of 73.1% (60.9, 83.2) and specificity of 70.2% (60.4, 78.8) in predicting CFLD. A 50% increase in APRI was associated with a 2.4-fold (95% CI: 1.7, 3.3) increased odds of having CFLD. APRI demonstrated full agreement with histology staging 37% of the time, but was within one stage 73% of the time. Only FIB-4 predicted portal hypertension at diagnosis (area under the receiver operator characteristic curve [AUC 0.91; P<0.001). CONCLUSION: This is the first liver biopsy-validated study of APRI and FIB-4 in pediatric CFLD. APRI appears superior to FIB-4 in differentiating CFLD versus CFnoLD. APRI also exhibited a high AUC in predicting severe liver fibrosis with specific cutoffs for lower stages.

Unrecognized hepatitis B in pre-screened children with hematologic and oncologic conditions.

BACKGROUND: This study evaluates the effectiveness and interpretation of hepatitis B (HBV) screening in an at-risk cohort of children with cancer or blood disorders. PROCEDURE: We conducted a retrospective epidemiologic analysis of children who screened positive for HBV (HBsAg, HbcAb) from 1999 to 2009 at a quaternary children's hospital, focusing on patients with hematologic and oncologic conditions. Descriptive statistics were generated for demographics and serologies. Follow-up of positive serologies and clinical outcomes were analyzed. RESULTS: A total of 12,754 children were screened for HBV. Of 391 that screened positive, 118 had a hematologic or oncologic diagnosis. Leukemia, anemia, and thrombocytopenia comprised 84% of diagnoses. The majority (98%) tested HBcAb positive but only 20% received confirmatory HBV DNA testing. Three patients (13% of those HBV DNA tested) were identified to have chronic disease. HBV was not a known pre-existing condition, and chemotherapy preceded HBV diagnosis in all cases. CONCLUSIONS: The majority of children with cancer or blood disorders who screened HBV positive did not receive follow-up DNA testing, exposing them to reactivation risk and delaying definitive therapy. HBcAb may be the only indicator of chronic HBV infection and DNA confirmation should be routine. Our findings suggest a significant number of additional patients eligible for HBV treatment may have been identified with reflexive DNA testing.

Impact of terrorism on health and Hospital Anxiety Depression Scale screening in medical students, Karachi, Pakistan.

OBJECTIVES: To determine the association of terrorism with psychiatric morbidity by Hospital Anxiety Depression scale among medical students in Karachi, Pakistan. METHODS: The questionnaire based cross-sectional survey was conducted from February to March 2011 and comprised students of the Institute of Physical and Medical Rehabilitation and the Dow Medical College, Dow University of Health Sciences, Karachi. The study tool was a validated Hospital Anxiety Depression scale questionnaire. The data was analysed on SPSS 16. Factor analysis was performed to check which factors had the most influence. RESULTS: Overall there were 1036 respondents. The impact of terrorism on physical, social and mental health was 40 (3.9%), 178 (17.2%) and 818 (79%) respectively. There was an association of terrorism in 980 (84.6%) respondents with psychiatric morbidity. CONCLUSION: There was an association of terrorism with psychiatric morbidity in majority of respondents. The significant risk factors were age, gender, physical, mental and social health and the desire to live in Pakistan.

Frequent factors for women and children subjected to sexual assaults presenting at Jinnah Postgraduate Medical Center, Karachi.

OBJECTIVES: To determine the frequent factors in women and children subjected to sexual assaults seeking medical care at Jinnah Postgraduate Medical Center, Karachi. METHODS: A cross sectional study was conducted in the Medico legal Department of Jinnah Postgraduate Medical Center, Karachi, Pakistan. Sexual assault victims seeking medical care and medico legal reports from Jan 2007-June 2010 were included in the study. The sampling technique was non-probability purposive. All women were informed regarding the confidentiality of their records and written informed consent was taken. In case of female children the consent was taken from both parents/guardians. The data was analyzed on statistical package for social sciences version 15. RESULTS: There were 180 women and children examined and interviewed after the Sexual assault. The mean age (years) was 19.24 +/- 7.33. Mostly reported victims were raped and abused both 162 (90%) and only rape was reported in 18 (10%).The physical, local, Abdominal and Pelvic examination showed fresh act of violence in sexual assault victims in 83 (46.1%) cases. The sexual assault was confirmed in 75 (41.7%) cases. CONCLUSION: The fresh sexual assault acts confirmed in 41%. The frequent factors in women and children subjected to sexual assaults were adult women (18-40 Years), two third victims brought by police after 6-24 hours of rape, 90% reported both sexual assault and physical violence, in two third cases no weapon used and no external marks of body injuries observed.

Effects of baby-friendly hospital initiative on breast-feeding practices in sindh.

OBJECTIVE: To determine changes in the breastfeeding practices of mothers after receiving counseling on 'Ten Steps to Successful Breastfeeding' as defined by the Baby Friendly Hospital Initiative comparing baby friendly hospitals (BFHs) and non-baby-friendly hospitals in Sindh, Pakistan. METHODS: The observational study was conducted from June 2007 to June 2009 in randomly selected baby-friendly and non-baby-friendly hospitals of Sindh, Pakistan. Non-probability purposive sampling was employed.The maternity staff was trained on 'Ten Steps to Successful Breastfeeding.'The changes in breastfeeding practices were analysed by SPSS version 15. RESULTS: A total of 236 women were included in the study. Of them, 196 (83.05%) were from baby-friendly hospitals and 40 (16.94%) from non-baby-friendly hospitals. Besides, 174 (88.7%) mothers in baby-friendly hospitals and 5 (12.5%) in non-baby-friendly hospitals during antenatal care received counseling by healthcare providers.There was an increase in breastfeeding practice up to 194 (98.97%) in the first category compared to 12 (30%) in the other category. CONCLUSION: Counseling under the Baby Friendly Hospital Initiative improved breastfeeding practices up to 98.97% in baby-friendly compared to non-baby-friendly hospitals.

Ciprofloxacin resistance and tolerance of Pseudomonas aeruginosa ocular isolates.

PURPOSE: Tolerance to antibiotics may occur due to changes in bacterial growth patterns and can be a precursor to development of resistance. However, there is a lack of information on the ability of ocular bacteria isolates to develop tolerance. This paper explores the tolerance to 8 different antibiotics of 61 microbial keratitis isolates of Pseudomonas aeruginosa from Australia and India using the MBC/MIC ratio, with tolerance defined by a ratio ≥ 32, and tolerance to ciprofloxacin by an agar diffusion assay. METHODS: Antibiotics used were ciprofloxacin, levofloxacin, gentamicin, tobramycin, piperacillin, imipenem, ceftazidime and polymyxin B. Isolates were sourced from microbial keratitis infections in Australia and India. Minimum bactericidal and minimum inhibitory concentration (MBC and MIC) were obtained using broth microdilution and compared to breakpoints from the Clinical Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) to determine bacterial susceptibility. Tolerance was assessed as MBC/MIC ≥ 32. An alternative method for tolerance detection (TD) was assessed with 13P. aeruginosa sensitive isolates by agar disk diffusion assay of ciprofloxacin followed by application of glucose to the agar and observation of re-growth of colonies. RESULTS: Thirty-three isolates were resistant to imipenem, 20 to ciprofloxacin, 14 to tobramycin and piperacillin, 12 to levofloxacin and ceftazidime, 8 to gentamicin, and 5 to polymyxin B. The percentage of strains resistant to levofloxacin (7 vs 30 %; p = 0.023), gentamicin (0 vs 24 %; p = 0.005) and tobramycin (4 vs 33 %; p = 0.004) was significantly greater in isolates from India.On average, strains from India exhibited notably greater MIC and MBC values compared to strains obtained from Australia. Out of 61 isolates, none displayed an MBC/MIC ratio ≥ 32. However, three sensitive isolates had low tolerance, nine had medium tolerance and one had high tolerance to ciprofloxacin with the TDtest. CONCLUSIONS: This study used two methods to determine whether P. aeruginosa strains could show tolerance to antibiotics. Using the MBC/MIC criteria no strain was considered tolerant to any of the eight antibiotics used. When 13 strains were tested for tolerance against ciprofloxacin, the most commonly used monotherapy for keratitis, one had high tolerance and nine had medium tolerance. This demonstrates the capacity of P. aeruginosa to develop tolerance which may result in therapeutic failures if inappropriate dosing regimens are used to treat keratitis.

Spectrum of SARS-CoV-2-Related Clinical Syndromes in Children: A Year in the Life.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a wide pediatric clinical spectrum. Initial reports suggested that children had milder symptoms compared with adults; then diagnosis of multisystem inflammatory syndrome in children (MIS-C) emerged. We performed a retrospective cohort study of hospitalized patients at a children's hospital over 1 year. Our objectives were to study the demographic and clinical profile of pediatric SARS-CoV-2-associated diagnoses. Based on the clinical syndrome, patients were classified into coronavirus disease 2019 (COVID-19; non-MIS-C) and MIS-C cohorts. Among those who tested positive, 67% were symptomatic. MIS-C was diagnosed in 24 patients. Both diagnoses were more frequent in Caucasians. Both cohorts had different symptom profiles. Inflammatory markers were several-fold higher in MIS-C patients. These patients had critical care needs and longer hospital stays. More COVID-19 patients had respiratory complications, while MIS-C cohort saw cardiovascular involvement. Health care awareness of both syndromes is important for early recognition, diagnosis, and prompt treatment.

Susceptibility of Contact Lens-Related Pseudomonas aeruginosa Keratitis Isolates to Multipurpose Disinfecting Solutions, Disinfectants, and Antibiotics.

Purpose: This study analyzed the susceptibilities of 17 contact lens (CL)-related keratitis isolates of Pseudomonas aeruginosa from Australia to antibiotics, multipurpose contact lens disinfecting solutions (MPDS), and disinfectants through minimum inhibitory (MIC) and minimum bactericidal concentrations. Methods: Antibiotics included ciprofloxacin, levofloxacin, gentamicin, tobramycin, piperacillin, imipenem, ceftazidime, and polymyxin B. The MPDS OPTI-FREE PureMoist, Complete RevitaLens OcuTec, Biotrue, and Renu Advanced Formula and the constituent disinfectants; alexidine dihydrochloride, polyquaternium-1, polyaminopropyl biguanide, and myristamidopropyl dimethylamine (Aldox) were analyzed. The combined susceptibility of disinfectants based on the MPDS formulation was assessed through fractional inhibitory concentration. Results: All isolates were susceptible to levofloxacin and gentamicin, 2/17 were resistant to ciprofloxacin; 1/17 was resistant to tobramycin, piperacillin, and polymyxin; and 3/17 were resistant to ceftazidime whereas 12/17 were resistant to imipenem. Of the four MPDSs, for Renu Advanced Formula 8/17 strains have an MIC ≤ 11.36 for OPTI-FREE PureMoist 14/17 strains have an MIC ≤ 11.36% for Complete RevitaLens 9/17 strains have an MIC ≤ 11.36, and for Biotrue 5/17 strains have MIC = 11.36. All strains were killed by 100% MPDS. At the concentrations used in the MPDSs, individual disinfectants were not active. From three tested isolates, no synergy was found in dual combinations of disinfectants. However, synergy was found for triple combination of disinfectants for three tested strains. Conclusions: Australian CL-related isolates of Paeruginosa were susceptible to most antibiotics. There was variability in susceptibility to different MPDS. Individual disinfectant excipients had limited activity. The combination of the disinfectants showed synergy, antagonism, and no interaction. Translational Relevance: This study will help to choose better preventive and treatment measures for microbial keratitis.

Antibiotic Resistance Characteristics of Pseudomonas aeruginosa Isolated from Keratitis in Australia and India.

This study investigated genomic differences in Australian and Indian Pseudomonas aeruginosa isolates from keratitis (infection of the cornea). Overall, the Indian isolates were resistant to more antibiotics, with some of those isolates being multi-drug resistant. Acquired genes were related to resistance to fluoroquinolones, aminoglycosides, beta-lactams, macrolides, sulphonamides, and tetracycline and were more frequent in Indian (96%) than in Australian (35%) isolates (p = 0.02). Indian isolates had large numbers of gene variations (median 50,006, IQR = 26,967-50,600) compared to Australian isolates (median 26,317, IQR = 25,681-33,780). There were a larger number of mutations in the mutL and uvrD genes associated with the mismatch repair (MMR) system in Indian isolates, which may result in strains losing their efficacy for DNA repair. The number of gene variations were greater in isolates carrying MMR system genes or exoU. In the phylogenetic division, the number of core genes were similar in both groups, but Indian isolates had larger numbers of pan genes (median 6518, IQR = 6040-6935). Clones related to three different sequence types-ST308, ST316, and ST491-were found among Indian isolates. Only one clone, ST233, containing two strains was present in Australian isolates. The most striking differences between Australian and Indian isolates were carriage of exoU (that encodes a cytolytic phospholipase) in Indian isolates and exoS (that encodes for GTPase activator activity) in Australian isolates, large number of acquired resistance genes, greater changes to MMR genes, and a larger pan genome as well as increased overall genetic variation in the Indian isolates.

Propylene glycol neurotoxicity due to sodium citrate therapy in an infant with renal tubular acidosis.

Sodium citrate in its liquid formulation is commonly used as therapy for renal tubular acidosis in pediatric patients. Convenient dosing and administration is important to ensure long-term medication adherence and normal growth in the chronic forms of this condition. Liquid sodium citrate formulations contain propylene glycol, a commonly used excipient, which can be toxic at high doses. Propylene glycol toxicity due to medication excipients has been reported in the literature, including many cases secondary to sustained exposure to intravenous anti-epileptics, however toxicity associated with oral sodium citrate therapy has not been described. We report the first case of propylene glycol neurotoxicity in a 6-week-old infant with renal tubular acidosis treated with sodium citrate. Clinical suspicion of risk for medication-related toxicity and awareness of propylene glycol content in sodium citrate led to timely diagnosis and management. Awareness of increased risk of toxicity in pediatric patients due to high sodium citrate requirement and low propylene glycol metabolism capacity is important for optimal care for pediatric patients with renal tubular acidosis.

Acquired fluoroquinolone resistance genes in corneal isolates of Pseudomonas aeruginosa.

Fluoroquinolones are widely used as an empirical therapy for pseudomonal ocular infections. Based on increasing reports on acquired fluoroquinolone resistance genes in clinical isolates of Pseudomonas aeruginosa, we investigated 33 strains of P. aeruginosa isolated from the cornea of microbial keratitis patients in India and Australia between 1992 and 2018 to understand the prevalence of acquired fluoroquinolone resistance genes in ocular isolates and to assess whether the possession of those genes was associated with fluoroquinolone susceptibility. Fourteen out of 33 strains were resistant to at least one fluoroquinolone. We obtained the whole genome sequence of 33 isolates using Illumina MiSeq platform and investigated the prevalence of two fluoroquinolone resistance genes crpP and qnrVC1. To examine the associated mobile genetic elements of qnrVC1 positive strains, we obtained long read sequences using Oxford Nanopore MinION and performed hybrid assembly to combine long reads with Illumina short sequence reads. We further assessed mutations in quinolone resistance determining regions (QRDRs) and antibiotic susceptibilities to ciprofloxacin, levofloxacin and moxifloxacin to examine the association between resistance genes and phenotype. Twenty strains possessed crpP in genetic islands characterised by possession of integrative conjugative elements. The qnrVC1 gene was carried by four isolates on class I integrons and Tn3 transposons along with aminoglycoside and beta-lactam resistance genes. We did not observe any evidence of plasmids carrying fluoroquinolone resistance genes. Resistance to fluoroquinolones was observed in those strains which possessed crpP, qnrVC1 and that had QRDRs mutations. The presence of crpP on its own was not associated with increased resistance to fluoroquinolones.

Bilateral adrenal haemorrhage: a cause of haemodynamic collapse in heparin-induced thrombocytopaenia.

Heparin-induced thrombocytopaenia (HIT) is a life-threatening complication of exposure to heparin. It is mediated by autoantibodies to platelet factor-4 causing platelet activation, destruction and thrombosis. Given their rich arterial supply and a single central vein, the adrenal glands are particularly susceptible to congestive haemorrhage following venous thrombosis. We report a case of bilateral adrenal haemorrhage (BAH) associated with HIT following prophylactic use of unfractionated heparin for venous thromboembolism causing adrenal insufficiency. BAH is a life-threatening paradoxical complication associated with HIT, a prothrombotic state. The resulting adrenal insufficiency can lead to haemodynamic collapse if unrecognised. Early diagnosis, in the wake of vague symptoms, and prompt treatment primarily aimed at repletion of glucocorticoids and close monitoring of enlarging haemorrhage is of utmost importance. Likewise, early identification of HIT is important to prevent potential complications including adrenal haemorrhage.

Reduced Pelvic Floor Muscle Tone Predisposes to Persistence of Lower Urinary Tract Symptoms after Puerperium.

Pregnant primiparous women at term were enrolled in the study. ICIQ-FLUTS questionnaire was used to find out prevalence of LUTS. MOS was used to assess pelvic floor muscle strength. Women were followed up after 8-10 weeks of delivery to find out remission or persistence of these symptoms. We found that increased frequency of micturition was the most common (82%) LUTS seen in primiparous women at term. More than half (51%) of these women who complained of LUTS had a poor pelvic floor muscle tone (MOS grade 3). Out of those who had symptoms during pregnancy 11% remained symptomatic even after puerperium. Interestingly 61% of those with persistence of symptoms demonstrated a very poor pelvic floor muscle tone at term (MOS grade 2), while the remaining 39% also had a tone of only MOS grade 3. Thus women with LUTS during pregnancy should be screened for their pelvic floor muscle tone with simple MOS system which will help to predict the persistence of these symptoms later on. Women with a low score (three or less) should be triaged for regular pelvic floor muscle exercises.

Hydrosalpinx as a Rare Presentation of Synchronous Ovarian and Endometrial Carcinoma - A Case Report.

Hydrosalpinx in postmenopausal woman is rare. Most commonly it is due to primary ovarian malignancy with fallopian tube involvement or primary fallopian tube carcinoma. But hydrosalpinx with no malignancy in the fallopian tube, associated with synchronous malignancy of ovary and endometrium is rare. In a postmenopausal women, hydrosalpinx is commonly due to fallopian tube malignancy or rarely pelvic inflammatory disease. We present a rare and very interesting case of 65-year-old nulliparous postmenopausal women with bilateral hydrosalpinx and pyometra who was found to have papillary serous adenocarcinoma of the ovary and endometroid adenocarcinoma of endomertrium with normal fallopian tube. One should always suspect genital malignancy with this presentation, especially in this age group.

An experience of teaching bioethics at secondary schools in Karachi.

Bioethics is the "critical analysis of emerging moral issues in health". The term was first used to refer to "the moral problems of the life sciences encompassing medicine, biology, environment, population and social sciences". Teaching bioethics is complex and challenging within multi-system educational program as in Pakistan for secondary schools. The objectives are difficult as bioethics teaching require changes in knowledge, skills and attitudes along with strong improvement in moral reasoning. The objectives of the study were to teach bioethics and evaluate comprehension and skills of ethical reasoning in students of secondary school in Karachi. This was a quasi-experimental study conducted in two schools (public and private-sector) of Karachi from January 2007 to December 2009. This was a preliminary study and used simple random sampling to recruit one hundred and ten students. The qualitative analysis of comprehension and skills were evaluated on numeric scales. The study found higher comprehension and skills level in females (66%) compared to male students during class-room sessions.

Determinants of lower extremity amputations: an institutional experience.

OBJECTIVE: To determine the determinants of lower extremity amputations in diabetics and non-diabetics in a tertiary care institute. STUDY DESIGN: Cross-sectional, analytical study. PLACE AND DURATION OF STUDY: Outpatients Department of the Institute of Physical Medicine and Rehabilitation, Dow University of Health Sciences, Karachi, from January 2007 to December 2010. METHODOLOGY: All patients with amputations reporting at the study centre for prosthesis fitting were included in the study. Patient`s age, level of amputation, stump complications and associated risk factors of amputation were recorded on a structured proforma. Prosthesis and orthotic assessment were carried out. The frequency and determinants were collected to compare diabetic and non-diabetic amputees. The data was analyzed in SPSS windows version 16. RESULTS: A total of 1091 subjects were provided prosthesis, including 847 males (77.6%). Mean age in diabetic and nondiabetics being 49.6 ± 15.2 and 26.6 ± 17.9 years respectively which is significant at (p < 0.001). Socioeconomic status and educational levels were significantly associated with diabetic status (p < 0.001). Amputation was more common in non-diabetic 858 (78.6%) compared to diabetics 233 (21.4%). CONCLUSION: This study has identified that most common and significant predictors were gender, low social status and educational levels. Other significant predictors of amputation identified were type of lesion, (infections and ischaemia), initial diagnosis acute/chronic arterial insufficiency and diabetic foot.

Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers.

MicroRNAs (miRNA) regulate complex patterns of gene expression, and the relevance of altered miRNA expression to ovarian cancer remains to be elucidated. By comprehensively profiling expression of miRNAs and mRNAs in serous ovarian tumors and cell lines and normal ovarian surface epithelium, we identified hundreds of potential miRNA-mRNA targeting associations underlying cancer. Functional overexpression of miR-31, the most underexpressed miRNA in serous ovarian cancer, repressed predicted miR-31 gene targets including the cell cycle regulator E2F2. MIR31 and CDKN2A, which encode p14(ARF) and p16(INK4A), are located at 9p21.3, a genomic region commonly deleted in ovarian and other cancers. p14(ARF) promotes p53 activity, and E2F2 overexpression in p53 wild-type cells normally leads via p14(ARF) to an induction of p53-dependent apoptosis. In a number of serous cancer cell lines with a dysfunctional p53 pathway (i.e., OVCAR8, OVCA433, and SKOV3), miR-31 overexpression inhibited proliferation and induced apoptosis; however, in other lines (i.e., HEY and OVSAYO) with functional p53, miR-31 had no effect. Additionally, the osteosarcoma cell line U2OS and the prostate cancer cell line PC3 (p14(ARF)-deficient and p53-deficient, respectively) were also sensitive to miR-31. Furthermore, miR-31 overexpression induced a global gene expression pattern in OVCAR8 associated with better prognosis in tumors from patients with advanced stage serous ovarian cancer, potentially affecting many genes underlying disease progression. Our findings reveal that loss of miR-31 is associated with defects in the p53 pathway and functions in serous ovarian cancer and other cancers, suggesting that patients with cancers deficient in p53 activity might benefit from therapeutic delivery of miR-31.