microRNA 21 and long non-coding RNAs interplays underlie cancer pathophysiology: A narrative review.

Non-coding RNAs (ncRNAs) are a diverse group of functional RNA molecules that lack the ability to code for proteins. Despite missing this traditional role, ncRNAs have emerged as crucial regulators of various biological processes and have been implicated in the development and progression of many diseases, including cancer. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two prominent classes of ncRNAs that have emerged as key players in cancer pathophysiology. In particular, miR-21 has been reported to exhibit oncogenic roles in various forms of human cancer, including prostate, breast, lung, and colorectal cancer. In this context, miR-21 overexpression is closely associated with tumor proliferation, growth, invasion, angiogenesis, and chemoresistance, whereas miR-21 inactivation is linked to the regression of most tumor-related processes. Accordingly, miR-21 is a crucial modulator of various canonical oncogenic pathways such as PTEN/PI3K/Akt, Wnt/ß-catenin, STAT, p53, MMP2, and MMP9. Moreover, interplays between lncRNA and miRNA further complicate the regulatory mechanisms underlying tumor development and progression. In this regard, several lncRNAs have been found to interact with miR-21 and, by functioning as competitive endogenous RNAs (ceRNAs) or miRNA sponges, can modulate cancer tumorigenesis. This work presents and discusses recent findings highlighting the roles and pathophysiological implications of the miR-21-lncRNA regulatory axis in cancer occurrence, development, and progression. The data collected indicate that specific lncRNAs, such as MEG3, CASC2, and GAS5, are strongly associated with miR-21 in various types of cancer, including gastric, cervical, lung, and glioma. Indeed, these lncRNAs are well-known tumor suppressors and are commonly downregulated in different types of tumors. Conversely, by modulating various mechanisms and oncogenic signaling pathways, their overexpression has been linked with preventing tumor formation and development. This review highlights the significance of these regulatory pathways in cancer and their potential for use in cancer therapy as diagnostic and prognostic markers.

Benzodiazepine use among adults residing in the urban settlements of Karachi, Pakistan: a cross sectional study.

BACKGROUND: There are hardly any studies carried out in Pakistan on the usage of benzodiazepines at the level of community. This research was aimed to determine the frequency of benzodiazepine use, along with its associations with socio-demographic and clinical characteristics among community dwelling adults, residing in two urban settlements of Karachi, Pakistan. METHODS: We performed a cross sectional study from August 2008 to December 2009, in 2 areas of Karachi, namely Garden and Sultanabad. We followed the systematic sampling strategy to randomly select the households, with an adult of either sex and of age 18 years or more. Data collection was carried out through interview, using a pre-tested questionnaire, with items on socio-demographic position, medical history and benzodiazepine use. Student's t-test and χ2 test was employed to determine the associations between socio-demographic and clinical characteristics, and their relationship with benzodiazepine use was determined using applied logistic regression. RESULTS: The overall percentage of benzodiazepine consumption was estimated to be 14%. There were significantly more benzodiazepine users in the peri-urban Sultanabad community to the urban community of Garden (p-value = 0.001). The mean age (± SD) for users was 51.3 (± 15.6) years compared to 37.1 (± 14.4) years among non-users. Bromazepam was the most widely used benzodiazepine (29%); followed by diazepam, with a median duration on primary use being 144 weeks (IQR = 48-240). The adjusted logistic regression model revealed that increasing age, location, female sex, unemployment and psychiatric consultation were associated with increased likelihood of benzodiazepine use. CONCLUSION: We believe the unregulated over-the-counter sales of benzodiazepines and social conditions might be playing a role in this high consumption of benzodiazepines in the community.

Antipsychotic treatment and weight gain: does risperidone behave differently in Pakistani psychiatric patients?

BACKGROUND: Studies from the Western world have shown that antipsychotic medications in psychiatric patients result in weight gain and other metabolic diseases. This study was undertaken to investigate whether any one of the five most commonly prescribed antipsychotics, (risperidone, olanzepine, trifluoperazine, quetiapine and haloperidol) could behave differently in terms of causing weight gain among patients attending the psychiatric outpatient clinics in a tertiary care hospital in Karachi, Pakistan. METHODS: For this retrospective cohort study, data were collected from outpatient records of the Aga Khan University Hospital, from 2003 to 2007. Demographic and clinical data were analysed. Repeated measures ANOVA, using a linear mixed model approach was used to assess weight gain over time due to the use of antipsychotic medications. RESULTS: A total of 124 subject records (68 males and 56 females) were evaluated. One-way ANOVA revealed that the groups being prescribed with antipsychotics were comparable with respect to age, duration of treatment and weight measurements. Frequencies were calculated which showed that weight increases significantly over time with respect to the prescribed antipsychotic medications, except for risperidone. Repeated measures ANOVA using the linear mixed model approach showed that the serial weight measurements were significantly different across the follow up times (p<0.05). CONCLUSION: Four of the commonly prescribed antipsychotic drugs do result in an increase in weight; however risperidone has no such effect, making it an option in-treating psychiatric disorders without worrying for any gain in weight. In view of the increased prevalence of obesity and other metabolic diseases, measures should be taken towards careful prescription of antipsychotic medications.

Outcome of cataract surgery at one year in Kenya, the Philippines and Bangladesh.

AIMS: To assess the change in vision following cataract surgery in Kenya, Bangladesh and the Philippines and to identify causes and predictors of poor outcome. METHODS: Cases were identified through surveys, outreach and clinics. They underwent preoperative visual acuity measurement and ophthalmic examination. Cases were re-examined 8-15 months after cataract surgery. Information on age, gender, poverty and literacy was collected at baseline. RESULTS: 452 eyes of 346 people underwent surgery. 124 (27%) eyes had an adverse outcome. In Kenya and the Philippines, the main cause of adverse outcome was refractive error (37% and 49% respectively of all adverse outcomes) then comorbid ocular disease (26% and 27%). In Bangladesh, this was comorbid disease (58%) then surgical complications (21%). There was no significant association between adverse outcome and gender, age, literacy, poverty or preoperative visual acuity. CONCLUSIONS: Adverse outcomes following cataract surgery were frequent in the three countries. Main causes were refractive error and preoperative comorbidities. Many patients are not attaining the outcomes available with modern surgery. Focus should be on correcting refractive error, through operative techniques or postoperative refraction, and on a system for assessing comorbidities and communicating risk to patients. These are only achievable with a commitment to ongoing surgical audit.

Association between antipsychotics and weight gain among psychiatric outpatients in Pakistan: a retrospective cohort study.

BACKGROUND: It has been known for a long time that use of antipsychotics, particularly atypical antipsychotics, is associated with weight gain and increase in risk of metabolic disturbances. In this study we have tried to find out if use of antipsychotics is associated with increase in weight and body mass index (BMI) in the Pakistani population. METHODS: We performed a case note review of all patients who had been prescribed antipsychotic medication at the psychiatry outpatient clinic of a tertiary care university hospital in Pakistan over a 4-year period. RESULTS: A total of 50% of patients had a BMI in the overweight or higher range at baseline. Patients showed a mean weight gain of 1.88 kg from baseline in 3 months and 3.29 kg in 6 months. Both of these values were statistically significant. The increase in mean BMI from baseline was 0.74 and 1.3 in 3 months and 6 months, respectively. In patients for whom we had at least one further weight measurement after baseline, 48% (39/81) showed a clinically significant weight gain. CONCLUSION: Pakistani patients are just as likely to put on weight during antipsychotic treatment as patients from other countries. Considering that this population already has a much higher prevalence of diabetes mellitus compared to the Western countries, the consequences of increased weight may be even more serious in terms of increased morbidity and mortality.

Consistency in the observation of features used to classify duct carcinoma in situ (DCIS) of the breast.

AIM: To determine interobserver and intra-observer agreement in the assessment of cytological grade and intraduct necrosis in pure duct carcinoma in situ (DCIS) of the breast. METHODS: Sixty unselected cases with illustrated diagnostic criteria were circulated to 19 practising histopathologists. RESULTS: Overall agreement was moderate for cytological grade in three categories: 71% agreement; weighted kappa (kappa w), 0.36; intraduct necrosis in three categories (absent, present, extensive): 76% agreement; kappa w, 0.57; and the Van Nuys classification system: 73% agreement; kappa w, 0.48. Agreement was no better among observers participating in the National External Quality Assurance Programme. Intra-observer agreement for cytological assessment (69.6% agreement; kappa w, 0.52) and intraduct necrosis (68.3% agreement; kappa w, 0.48) was moderate, suggesting that individual variation rather than precision of criteria contributes to the lack of agreement. CONCLUSIONS: Moderate agreement on observations can be achieved by non-specialist pathologists, with better agreement on necrosis than cytological grade. There was evidence of consistent individual bias towards over or under scoring cytological grade, which could be corrected with adequate and prompt feedback.

Juvenile xanthogranuloma of the nasal cavity.

Juvenile xanthogranuloma is a benign, normolipaemic, self-healing condition and a type of histiocytosis that occurs most frequently in infants and children. This condition usually presents with solitary or multiple cutaneous lesions and occasionally with visceral lesions. We report a case of juvenile xanthogranuloma occurring in the nasal cavity. We believe this is the first report, in the English literature, of juvenile xanthogranuloma occurring in this site.

Gastrostomy-related pancreatitis in a child: a fatal case.

A case of acute pancreatitis following gastrostomy feeding tube insertion is presented. This is a rare and fatal complication, which has not been described before. The role of the gastrostomy catheter and total enteral nutrition in the causation of acute pancreatitis is discussed. Pathologists and clinicians should be aware of this disastrous and potentially avoidable condition.

Primary osteosarcoma of the breast.

Osteosarcoma is a rare primary breast tumour. We report on a 55-year-old woman who presented with a left breast lump and a mammogram suggestive of carcinoma. At lumpectomy, a 3 cm mass was removed. Histology was consistent with primary osteosarcoma. There was satisfactory surgical clearance and no evidence of metastasis. She received four courses of adjuvant post-operative chemotherapy and remains free of disease at 14 months from diagnosis.

Brenner tumour of the vagina.

Polyps of the vagina are rare and are either of inflammatory/reactive or neoplastic origin. A case of extraovarian Brenner tumour of the vagina in a postmenopausal woman, who presented with a vaginal polyp, is described. The polyp was excised and on histological examination, had the triphasic pattern (transitional, glandular and stromal) characteristic of Brenner tumour. The histogenesis of Brenner tumour is discussed in the context of this unusual location and the controversy of its origin.

Unusual presentation of a nasal (antrochoanal) polyp.

A case is described of expulsion of an autoamputated antrochoanal nasal polyp per mouth in a young patient. This rare complication of a nasal polyp is potentially dangerous.

Sudden death following cesarean section for placenta previa and accreta.

A case of disseminated intravascular coagulation (DIC) in a young woman after cesarean section for placenta previa and accreta is presented. Evidence of extensive pulmonary embolization by trophoblastic tissue, together with microthrombi in the cerebral and pulmonary blood vessels, is found at autopsy. Awareness of this syndrome and prompt action are necessary to prevent tragic consequences.

Sudden death caused by giant cell myocarditis following coronary artery bypass.

An unusual case of idiopathic giant cell myocarditis (GCM) is described. The patient had a 5-year history of stable and unstable angina, poorly controlled by medical treatment. He underwent a successful coronary artery bypass, but 2 months later died suddenly at home. A coroner's autopsy revealed isolated GCM. This newly described possible association between the surgery and the condition is discussed and the pertinent literature is reviewed. We suggest that the list of causes of GCM in postoperative patients should also include foreign-body reaction. Our findings support the view that myocarditis occasionally masquerades as fatal acute myocardial infarction.

Malignant melanoma of penis and male urethra. Is it a difficult tumor to diagnose?

Two cases of malignant melanoma of the penis and male urethra are presented in which the diagnosis was difficult to make clinically and histopathologically. Our findings support the general opinion that melanomas at this site have a poor prognosis.

Histopathology: its role in the diagnosis of a child with intussusception.

Spontaneous expulsion of a small portion of the intestinal mucosa per rectum, in an infant, associated with ileocolic intussusception is an extremely rare condition. This appears to be the first report of such a clinical presentation. The initial diagnosis was raised by the histopathologist following examination of the eliminated piece of tissue. Subsequent barium enema and laparotomy confirmed the diagnosis and the ileocolic intussusception was successfully reduced. This unusual presentation, together with a review of the pertinent literature, is discussed. Our findings indicate that both the clinicians and histopathologists should be aware of this phenomenon and stress the importance of the histological examination of any unusual faecal matter. This may prove to be a simple, quick and cheap method of investigation of this condition.