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Objective: To ensure family spacing in our low socio-economic class. Study Design: Quasi-experimental study. Place and Duration of Study: Pak Emirates Military Hospital Rawalpindi, from Jan 2018 to Dec 2019. Methodology: Two hundred females using oral contraceptive pills for spacing of children coming to Pak Emirates Military Hospital were selected. The problems of using contraceptive pills were identified. Out of these 87 women agreed to choose an intrauterine copper device (IUCD). Results: Out of 200 women 87 converted from oral contraceptive pills to intrauterine copper device use. Most of them faced daily dosage problems 168 (84%). Nausea was encountered by 123 (61.5%) women and later settled in 89 (44.5%) women. About 31 (15.5%) were worried about the chances of uterine perforation and 56 (28%) were worried about lost intrauterine copper device resulting in laparotomy. About 65 (32.5%) were afraid of infection, backache and vaginal discharge. About 91 (45.5%) women thought to have gastric problems with the intrauterine copper device. About 71 (81%) agreed to have a spacing of children for about five years and removal whenever desired. Conclusion: Intrauterine contraception is a very safe and efficient method for contraception as compared to oral pills. If expertise is, available it should be used and couples should be fully educated for its safety.

Objective: To compare the effectiveness of mirror therapy and motor relearning program for improving the upper limb motor function in stroke patients. Study Design: A randomized control trial with registration number IRCT20200316046791N1 (IRCT). Place and Duration of Study: Al-Noor Hospital and Al Jannat Medicare, Rahim Yar Khan Pakistan, from Jan to Jul 2020. Methodology: Sample size consisted of 30 patients recruited by convenient sampling. Patients were randomized into two groups. Both groups received 5 sessions a week for 6 weeks. Group A received Motor Relearning Program while the treatment of group B was Mirror Therapy. Motor part of Fugl Meyer Assessment was used as an outcome measure. Non parametric Friedman test was used for within group analysis, while for between group analyses Karuskal-Wallis test was used. Results: The total participants who suffer from left hemiplegia were 22 whereas the patients having right hemiplegia were 8. The mean age of participants in both groups was 53.80 ± 7.6 group A median (interquartile range) at pre-assessment was 5.00 (3) at mid-assessment median=15.00 (4) while at post assessment median was 25.00 (6). Group B median at baseline was 6.00 (4), at mid-assessment median=14.00 (9), post assessment median was 17.00 (13). Mid and post assessment comparison showed both treatments improved the motor function. Statistically the results were non-significant (p>0.005). Both treatments improved the motor function in stroke patients. Conclusion: There is no significant difference between the effectiveness of Mirror Therapy and Motor relearning program in improving the upper limb motor function of stroke patients.

Background: The aim of current study was exploring the ocular abnormalities in individuals with Type 1 & 2 diabetes. Methods: Patients referred for diabetic ocular abnormalities (retinopathy, cataract, glaucoma and refractive error) on fundoscopy from LRBT eye hospital Korangi, Karachi were randomly included in the study. Retinopathy, cataract and refractive error were evaluated by slit lamp biomicroscope or indirect ophthalmoscope, & categorized into lacking, non-proliferative, proliferative retinopathy, maculopathy, capsular or sub capsular cataract, myopia and hypermetropia. While glaucoma was assessed by tonometry. Prevalence of eye complication has been seen in subjects. Outcome of substantial risk factors on the diverse phases of retinopathy, multivariate regression analysis was performed. Results: 200 diabetic subjects (106 males and 94 females) when the compared; diabetic subjects and subjects with hypertension; 28.0 % retinopathy, 9.75 % cataract, 7.31 % with glaucoma, and about 2.43% refractive error were found out among the diabetic males. 47.61 % retinopathy, 11.9% Cataract, 40.47% refractive error were found in females. In males with diabetes and hypertension were found 60.46 % retinopathy, 27.9 5% cataract, 11.62 % refractive error & in females 46.15% retinopathy, 19.23 % cataract, and 34.61 % with refractive error. Conclusions: This current study emphasizes screening of diabetic subjects regularly so as to distinguish ocular abnormalities and increasing public awareness.

Objective: To find the association of preterm delivery with metabolic syndrome in females presenting in a tertiary care hospital.Study Design: Cohort study.Place and Duration of Study: Department of Obstetrics & Gynecology, Combined Military Hospital Kharian, from May 2020 to Oct 2020.Methodology: A total of 150 females fulfilling inclusion criteria were enrolled in the study which were divided into two equal groups ‘A’ and ‘B’. Group ‘A’ was with metabolic syndrome and group ‘B’ without it. These females were followed in OPD till active labor, assessed and followed till delivery of fetus. If delivery occurred before 37 weeks, then preterm delivery was labeled. All this information was recorded on a pre-designed proforma.Results: The risk for preterm delivery was 2.18 times higher in group ‘A’ as compared to group ‘B’. (Relative Risk = 2.18, CI (95%) 1.1529 - 4.12).Conclusion: There is a strong association of preterm delivery with metabolic syndrome in females.

BACKGROUND Cerebrovascular event is the most common reason of acute neurological injury in the western world. There is an extensive literature and data available on its prognosis, outcomes and complications rates from the west, yet still, data regarding its safety and efficacy is scarce from the South Asian belt. OBJECTIVE To elucidate the role of carotid endarterectomy in patients with carotid stenosis regarding prevention of stroke and safety of the procedure. METHODS A descriptive case series of 335 consecutive patients from January 1990 till July 2018. All patients who underwent carotid endarterectomy were included. Patient having asymptomatic carotid disease (≥90%), history of a transient ischemic attack or patients with a recent or previous episode of ischemic stroke (≥60%) were selected for the procedure. All procedures were performed under GA. Post operatively patients were kept on antiplatelet therapy and followed on outpatient basis for any complications using carotid duplex scans. Data regarding 30-day postoperative parameters of the procedure were collected and evaluated. P< 0.05 is considered significant. RESULTS A total of 335 carotid endarterectomies were performed. The majority of patients in our series were males 68.90% (n = 230) compared to 31.10% (n = 105) females (P< 0.05). There were no intraoperative mortalities in our patients. The 15-day perioperative mortality was 1.5% (n = 5), out of which 3 patients had concomitant CABG and died of cardiac complications. The mortality rate of CEA alone was 0.6% (n = 2). Six patients (1.8%) developed focal neurological deficits in the postoperative period during the hospital stay. Three patients developed wound infection after surgery. Neck hematoma formation occurred in 11.7% (n = 39) patients and 7 required immediate decompression. A total of 321 patients remained stroke free at 6 months follow up. There was no increased risk of stroke secondary to bilateral carotid disease (OR 1.9 CI 0.35-10.7 P= 0.44). CONCLUSION Carotid Endarterectomy is a relatively safe and effective procedure in our large series from Pakistan. It remains the standard for management of carotid stenosis in symptomatic as well as asymptomatic patients with critical stenosis.

Hepatitis D virus (HDV) is a dependent virus that relies on hepatitis B virus for its replication and transmission. Chronic hepatitis D is a severe form of viral hepatitis that can result in end stage liver disease. Currently, pegylated interferon alpha is the only approved therapy for chronic HDV infection and is associated with significant side effects. Liver transplantation (LT) is the only treatment option for patients with end-stage liver disease, hepatocellular carcinoma, or fulminant hepatitis due to coinfection with HDV. As LT for HDV and hepatitis B virus coinfection is uncommon in the United States, most data on the long-term impact of LT on HDV are from international centers. In this review, we discuss the indications and results of LT with treatment options in HDV patients.

Thyroid nodules are commonly diagnosed in the general population. Though the majority of them are benign and followed clinically once detected, if compressive symptoms arise or malignancy is diagnosed, then surgical excision is considered the standard treatment. As surgery is associated with various post-operative complications, newer less invasive techniques have gained popularity. This article presents the various percutaneous ablation techniques that are currently being used for thyroid nodules. In recent years, several studies largely from Asian and Europe institutions have shown promising results with the use of radiofrequency ablation (RFA), ethanol ablation (EA), and laser ablation (LA) for thyroid nodules. These techniques are gaining more acceptance worldwide as an alternative to surgery. Comparatively newer techniques such as microwave ablation (MWA) and high-intensity focus ultrasound (HIFU) are also available but there is little evidence about their efficacy. Percutaneous ablation techniques with a promising safety profile can be an effective alternative to traditional surgical methods for the management of carefully selected thyroid nodules. However, large-scale randomized control trials are needed to establish the efficacy and safety of these techniques in the North American population.

Objective: To assess the knowledge, attitude and practices of first aid management among school teachers of Karachi. Study design and setting: This cross-sectional study was conducted at 4 schools in Karachi, from April to September 2018. Methodology: School teachers of class 1st to class 8th were included and teachers of coaching centers and academies were excluded. Data was collected through non-probability, convenient sampling technique. Data was obtained using aselfadministered closed-ended questionnaire. Data was entered and analyzed using SPSS version 23. Frequencies were calculated. Informed consent was obtained and anonymity of the subjects was maintained. Results: Total 162 participants aged 20-40 years participated in this study.Among the participants, 84% were females. Participants had inadequate knowledge of first aid and attitude towards first aid management was found to be positive and more than 90% of the respondents were ready to be trained for First Aid management. Data showed unsatisfactory results to manage common childhood injuries at school.Most of participants had poor knowledge regarding the management of epistaxis, choking, fainting and knocked out tooth. Conclusion: Although the overall attitude of the school teachers regarding first aid practices was favorable, levels of knowledge as well as practice of first aid found to be inadequate and many recognized the need for the introduction of the formal first aid training program at the school level

COVID-19 may manifest as mild, moderate or severe disease with each grade of severity having its own features and post-viral implications. With the rising burden of the pandemic, it is vital to identify not only active disease but any post-recovery complications as well.This study was conducted with the aim of identifying the presence of post-viral symptomatology in patients recovered from mild COVID-19 disease. Presence or absence of eleven post viral symptoms was recorded and we found that eight of the eleven studied symptoms were notably more prevalent amongst the female sample population. Our results validate the presence of prolonged symptoms months after recovery from mild COVID-19 disease, particularly in association with the female gender. Hence, proving the post-COVID syndrome is a recognizable diagnosis in the bigger context of the post-viral fatigue syndrome.

Biased evaluation fears and paranoid thoughts lead to various safety behaviors that are the cardinal features and perpetuating factors of social anxiety. The present study aimed to emphasize evaluative and paranoid thoughts that predispose and maintain this growing psychological condition. A cross-sectional research design was employed to explore the relationship between social comparison, paranoid social cognitions, and submissive behaviors in patients with social anxiety. Furthermore, predictive effects of social comparison and paranoid ideation on submissiveness, along with mediating factors, were assessed in a clinical sample. The study sample consisted of 100 treatment-seeking female patients of social anxiety (M = 25.21 years), recruited through purposive sampling. The findings revealed significant correlations between social comparison, paranoid social cognitions, and submissive behaviors. Rank, a subscale of social comparison, and paranoid social cognitions turned out as predictive factors of submissive behaviors. A novel finding is that paranoid social cognitions mediate the relationship between social comparison and submissive behaviors in socially anxious individuals. Study results will assist clinicians to devise effective management plans for patients by comprehending possible causes of submissiveness and considering paranoid ideation as a manifestation of social anxiety.

Effective restoration of extensive tracheal damage arising from cancer, stenosis, infection or congenital abnormalities remains an unmet clinical need in respiratory medicine. The trachea is a 10–11 cm long fibrocartilaginous tube of the lower respiratory tract, with 16–20 tracheal cartilages anterolaterally and a dynamic trachealis muscle posteriorly. Tracheal resection is commonly offered to patients suffering from short-length tracheal defects, but replacement is required when the trauma exceeds 50% of total length of the trachea in adults and 30% in children. Recently, tissue engineering (TE) has shown promise to fabricate biocompatible tissue-engineered tracheal implants for tracheal replacement and regeneration. However, its widespread use is hampered by inadequate re-epithelialisation, poor mechanical properties, insufficient revascularisation and unsatisfactory durability, leading to little success in the clinical use of tissue-engineered tracheal implants to date. Here, we describe in detail the historical attempts and the lessons learned for tracheal TE approaches by contextualising the clinical needs and essential requirements for a functional tracheal graft. TE manufacturing approaches explored to date and the clinical translation of both TE and non-TE strategies for tracheal regeneration are summarised to fully understand the big picture of tracheal TE and its impact on clinical treatment of extensive tracheal defects.

Introduction Acute appendicitis (AA) is the most common cause of acute abdomen in young adults. The diagnosis is usually made on various clinical findings. However, a missed case of acute appendicitis is a catastrophe as it later presents with life-threatening complications and results in medicolegal issues. Raised total leukocyte count (TLC) is a frequent finding in patients with acute appendicitis. As a convention, a normal leukocyte count usually rules out the differential diagnosis of acute appendicitis. Recent studies claimed that a substantial proportion of patients with normal TLC also had acute appendicitis and warranted a careful evaluation of such cases before sending them home. However, the reported frequency of acute appendicitis among TLC normal patients varied greatly among studies which necessitated the present study. Aim Our aim was to determine the frequency of acute appendicitis in patients of normal TLC. Materials and methods This descriptive cross-sectional study was conducted at the Department of Surgery, KRL Hospital Islamabad. This study was carried out from 1 July 2019 to 31 December 2019. This study involved 238 patients of both genders aged between 12 and 70 years suspected of acute appendicitis on physical and ultrasound findings but with a normal TLC (4,500-11,000 WBCs/µL). The outcome variable was the frequency of acute appendicitis among such patients which was diagnosed upon surgery (inflamed appendix with free fluid) and histopathology of excised tissue (mucosal inflammation, neutrophil infiltrates, wall necrosis). Frequency of acute appendicitis was compared across various age and gender groups. Written informed consent was obtained from every patient. Results The mean age of the patients was 27.4±15.5 years. Majority (n = 167, 70.2%) of the patients were aged ≤25 years, followed by 40 (16.8%) patients aged ≥46 years and 31 (13.0%) patients aged between 26 and 45 years. There were 135 (56.7%) male and 103 (43.3%) female patients with a male to female ratio of 1.3:1. All of the patients (100.0%) had pain in the right iliac fossa (RIF) while rebound tenderness, anorexia, nausea/vomiting, fever and dysuria were noted in 83.6%, 79.0%, 73.9%, 63.9% and 15.1% patients, respectively. The diagnosis of acute appendicitis was made in 198 (83.2%) patients with normal TLC and suspicion of acute appendicitis on physical findings and ultrasound. When stratified, there was no statistically significant difference in the frequency of acute appendicitis across various age (p-value = 0.988) and gender (p-value = 0.913) groups. Conclusion In the present study, contrary to the routine impression that normal TLC rules out the differential diagnosis of acute appendicitis, a substantial proportion of patients with clinical and ultrasound suspicion of acute appendicitis but normal TLC had acute appendicitis which is worrisome as a missed case may later present with complications. The present study thus warrants cautious evaluation of clinically suspected cases with normal TLC count to avoid a missed appendicitis and improve the outcome in future surgical practice.

An autoimmune neuromuscular junction disorder, myasthenia gravis, occurs when antibodies are produced against postsynaptic membrane acetylcholine receptors. Late-onset myasthenia gravis, a rare variant of the disease found in the elderly, has become a diagnostic challenge on account of its atypical presentation. We proffer a case of a 60-year-old man that presented with progressive dysphonia and weakening of cough, which was eventually followed by difficulty in swallowing and nasal regurgitation. Examination and laboratory workup came out unremarkable apart from a positive acetylcholine receptor antibody test, due to which a diagnosis of laryngeal myasthenia, an uncommon presentation of late-onset myasthenia gravis was made. Following treatment with pyridostigmine and prednisolone saw a relief of the active complaints. This article highlights the need for physicians to stay alert and have a high suspicion of such probability for timely diagnosis.

OBJECTIVE Autonomously functioning thyroid nodules (AFTNs) have long been treated with either surgery or radioactive iodine (RAI). Being an invasive procedure, even thyroid lobectomy for this condition is associated with complications such as anesthesia side effects, scarring, iatrogenic hypothyroidism, and injury to other structures. Similarly, RAI is associated with hypothyroidism and may require multiple courses. Therefore, minimally invasive techniques such as radiofrequency ablation (RFA) are being advocated as an alternative treatment for AFTNs. To date, only few studies have been published on this topic and are largely on European and Asian populations. The aim of this review is to assess the efficacy and safety of RFA as a potential alternative for treatment of AFTNs compared to conventional surgery and radioiodine. METHODS/STUDY DESIGN Comprehensive PubMed and Embase searches were performed using the following terms such as (autonomously functioning thyroid nodules and radiofrequency ablation), (radiofrequency ablation and hyperthyroidism), and (radiofrequency ablation and toxic thyroid nodule). Both prospective and retrospective studies were included based on the inclusion and exclusion criteria specified in the text. RESULTS Initially, 57 studies were identified and after excluding 47 studies, finally 10 studies were included in the review. CONCLUSION Although surgery remains the first line treatment for AFTN. However, RFA is a safe option compared to RAI or surgery, especially in patients who are high-risk surgical candidates or have absolute contraindications to RAI. Currently, trials with follow-up greater than or equal to 5 years are warranted. It will aid in formulating a standardized surveillance protocol and also generalize RFA's use for AFTN. Laryngoscope, 2021.

The incidence of tuberculosis (TB) is many fold higher in transplant recipients than in the general population with the highest risk in first year post-transplant. The purpose of this review is to describe the epidemiology, clinical characteristics, management, and outcomes of TB in organ transplant recipients from TB endemic regions and highlight the challenges faced in their management. TB can be increasingly difficult to diagnose and manage in transplant recipients. Clinical manifestations are often atypical leading to delay in diagnosis and available diagnostic modalities are limited in their ability to accurately detect TB. Moreover, the treatment of TB is particularly difficult owing to drug–drug interactions with post-transplant medications. Hence, the focus of recent research has been identification and treatment of latent TB infection pre-transplant. The prevalence of TB in transplant recipients is reportedly 12% in TB endemic countries compared to 5% in developed countries. The risk is greatest among transplant recipients with residence in a country with high TB burden. The clinical presentation can vary from the classic symptoms to unusual extrapulmonary manifestations, particularly involvement of genitourinary tract in renal transplant recipients. The first-line treatment is similar to that for immunocompetent patients but requires greater vigilance in monitoring of side effects, particularly hepatotoxicity. Longer treatment duration may be needed in those in whom a first-line regimen could not be used or those with drug-resistant TB. All transplant recipients should be screened for latent TB infection (LTBI) and given prophylaxis if found to have evidence of LTBI.

Background Thyroid nodules are commonly being diagnosed in general population and have a potential for malignant transformation. Historically, surgery has been considered as the first line treatment for these tumors. However, with passage of time newer minimally invasive techniques such as RFA (radiofrequency ablation) has been adapted. Though, RFA for thyroid tumors has been performed more commonly in Asian and European countries, it is a fairly new technique in North America. The aim of the review is to assess the current data and conclude that whether RFA is likely a valuable option when compared to surgery for treatment of thyroid tumors. Materials and methods A Comprehensive PubMed/MEDLINE, Embase and Web of Science search was performed. To expand our search, references of the retrieved articles were also screened for additional data. After selecting the studies that fulfilled the initial screening, authors independently reviewed the selected studies and screened the full texts to identify those that met the inclusion criteria. Results The comprehensive literature search from PubMed/MEDLINE, Web of Science, and EMBASE databases revealed 1094 studies (Embase 870, PubMed 200, and Web of Science 24). References were imported for screening. Amongst 1094 studies, 138 duplicates removed, and 956 studies were screened against title and abstract. After these 777 studies were excluded the remaining 179 studies were assessed for full-text eligibility. Amongst them 127 studies excluded due to wrong design or setting. Finally, 18 studies were included in the review. Conclusion RFA appears to be a safe alternative to surgery in selected cases. However, it is not widely used and there are few randomized controlled trials. Furthermore, it is associated with a low risk profile and has shown promising results in patients who are difficult surgery candidates. Currently large-scale prospective studies are needed in North America to establish the efficacy of RFA and its use as an alternative to surgery for thyroid tumors.

Recurrent Laryngeal papillomatosis (RLP) is a disease of the aero-digestive junction superimposed at the upper respiratory tract. Low risk human papillomavirus type 6 and 11 are infectious agents in RLP. Mainstay of treatment for RLP is CO2 laser vaporization for debulking of papilloma. Understanding of the gene changes at expression level might prove helpful for RLP management. The study was designed to evaluate the changes in tumorigenesis genes in RLP cases to mark the severity and aggression at gene expression level for disease management. Tissue samples and peripheral blood samples were acquired from clinically diagnosed RLP patients of age

Malaria is caused by Plasmodium parasite. It is transmitted by female Anopheles bite. Thick and thin blood smears of the patient are manually examined by an expert pathologist with the help of a microscope to diagnose the disease. Such expert pathologists may not be available in many parts of the world due to poor health facilities. Moreover, manual inspection requires full concentration of the pathologist and it is a tedious and time consuming way to detect the malaria. Therefore, development of automated systems is momentous for a quick and reliable detection of malaria. It can reduce the false negative rate and it can help in detecting the disease at early stages where it can be cured effectively. In this paper, we present a computer aided design to automatically detect malarial parasite from microscopic blood images. The proposed method uses bilateral filtering to remove the noise and enhance the image quality. Adaptive thresholding and morphological image processing algorithms are used to detect the malaria parasites inside individual cell. To measure the efficiency of the proposed algorithm, we have tested our method on a NIH Malaria dataset and also compared the results with existing similar methods. Our method achieved the detection accuracy of more than 91% outperforming the competing methods. The results show that the proposed algorithm is reliable and can be of great assistance to the pathologists and hematologists for accurate malaria parasite detection.

HPPD gene codes a dioxygenase enzyme involved in catalysis of different molecules such as tyrosine and phenylalanine by oxidizing them to produce energy. A single change in protein can trigger serious genetic disorders like Tyrosinemia type III and Hawkinsinuria. This study aims to identify the functional missense SNPs of the HPPD gene by using multiple computational tools. All deleterious missense SNPs retrieved from Ensembl and OMIM database were evaluated through six different software. Ultimately, out of 148 missense SNPs, only 27 were confirmed as diseasecausing SNPs by developing a consensus approach. These damaging SNPs were further examined to evaluate their impact on protein stability and energy including their evolutionary conservation. Native and mutated proteins structures were also designed and superimposed by I-TASSER and PyMol respectively. This work results in narrowing down missense SNPs which are still not confirmed experimentally and demands the confirmation by GWAS data. Thus, these missense SNPs could directly or indirectly destabilize the amino acid interactions causing functional deviations of protein.

Patient: Female, 80 Final Diagnosis: Diffuse alveolar hemorrhage in influenza A viral pneumonia Symptoms: Generalized fatigue • shortness of breath Medication: — Clinical Procedure: — Specialty: Critical Care Medicine Objective: Rare co-existance of disease or pathology Background: Diffuse alveolar hemorrhage (DAH) represents a life-threatening complication for many respiratory infections. We present a case of a patient with influenza A pneumonia associated with DAH. Case Report: An 80-year-old female patient was admitted with lethargy, dyspnea, and chest pain. On examination, she was afebrile with bilateral basal inspiratory crackles. Her chest x-ray revealed retro-cardiac infiltrate. Her hospital course was complicated by respiratory failure and septic shock requiring intubation. Nasopharyngeal swabs, rapid testing was positive for influenza A. Bronchoscopy showed diffuse bleeding and bronchoalveolar lavage (BAL) of the left lower lobe showed progressively bloody returns, consistent with DAH. Methylprednisolone 250 mg daily was started, with improvement in oxygenation. Repeat bronchoscopy 2 days later revealed normal mucosa and no further bleeding. The patient’s respiratory status and infiltrates improved, but her overall status continued to deteriorate, and she died 2 weeks after admission. Conclusions: High fatality rates have been reported in patients with influenza A viral pneumonia complicated by DAH. Advanced age and the presence of significant co-morbidities might predispose a patient to the development of a more aggressive clinical manifestation of influenza A and also increases the risk of developing DAH. Therefore, clinicians managing patients with influenza A viral pneumonia with this predisposing history should also maintain a high suspicion for DAH. We suggest early BAL for diagnosis and for the evaluation of other infections etiologies. Aggressive supportive care and the use of antiviral agents is recommended. The role of steroids is unclear and can be considered in patients with fulminant disease but might have no outcome benefit.

Malignancies of the upper urinary tract are rare, accounting for about 8% of all malignancies of the renal system, presenting mostly as urothelial carcinoma. Squamous cell carcinoma (SCC) arising from the upper urinary tract is even more rare, accounting for about 0.5% of all malignancies of the renal system and 10% of all renal pelvic tumors. There are very few case reports in the indexed literature regarding renal squamous cell carcinoma. Here we present a case of SCC arising from the lower pole of left kidney, in a 35-year-old male resident of Muzaffarabad, Azad Kashmir.

Purpose Our present study was a qualitative investigation intending to explore the emotional journey of wives whose spouse has been diagnosed with Bipolar I Disorder, using a phenomenological design. Method Semi-structured face to face interviews were conducted with 5 wives of already diagnosed Bipolar I Disorder patients to uncover their lived experience in terms of the emotional journey they had had. For data analysis, we used Hycner’s explicitation process. Moreover, for data verification we employed the strategies of frequent debriefing sessions peer review and member checks. Results Our analysis revealed six major themes encapsulating the participants emotional journey. These included Shock, Betrayal and the Incomprehensible, Apprehensions and Uncertainty, Anger and Irritability, Loneliness and Helplessness, Compassion and Acceptance and Reconciliation. Conclusion It became clear to us that wives of individuals diagnosed with Bipolar I Disorder are on a continuous emotional journey dealing with the burden, stress, complications, uncertainty and making many sacrifices along the way. Our study highlighted many culture specific factors of the phenomenon. This insightful exploration has opened up new horizons to conceptualize the challenges of wives dealing with an ailing spouse in the context of a Pakistani society.

Introduction Vitiligo is an acquired pigmentary disorder of the skin and mucous membranes which is characterized by circumscribed depigmented macules and patches. Vitiligo is a progressive disorder in which some or all of the melanocytes in the affected skin are selectively destroyed. Around 0.5-2% of the world population is affected by vitiligo and the average age of onset is 20 years. The objective of the study was to evaluate the efficacy of tacrolimus versus clobetasol in the treatment of vitiligo. It is an open randomized control trial conducted in the Department of Dermatology, Nishtar Hospital, Multan for six months. Methods One hundred sixty-two patients of vitiligo were included in the study. The disease was diagnosed on basis of clinical features and the Standard Assessment scale proposed by Hossain which was used to monitor and grade the response. Patients were randomly allocated into two groups by lottery method having 81 patients in each group. Group A was given tacrolimus whereas Group B was given clobetasol. Patients were followed up every four weeks. On the 12th week of treatment, effectiveness was assessed by measuring the Assessment scale proposed by Hossain. The results of the two groups were then compared. Results Sixty-three patients (38.9%) were males whereas 99 patients (61.1%) were females. The mean age of the patients included in the study was 29.68 + 8.162 years. The mean weight of the patients was 62.25 + 9.529 Kg. Out of 162, treatment was effective in 89 patients (54.9%) whereas in 73 patients (45.1%) the treatment was ineffective. In Group A (tacrolimus), 42 patients (51.9%) had effective treatment (on the complete resolution of symptoms) whereas 39 patients (48.1 %) had ineffective treatment. In Group B (clobetasol), 47 patients (58%) had effective treatment, and the rest (34, 42%) had ineffective treatment. A Chi-Square test was applied to compare the efficacy of the two groups. There was no statistically significant difference in both the groups in terms of efficacy. Group B was numerically superior in terms of effective treatment (47 versus 42) but not superior statistically. Conclusion Comparison of tacrolimus and clobetasol in patients of vitiligo showed no significant difference in the efficacy of the two groups. It can be concluded that tacrolimus may be considered superior to corticosteroids as its local and systemic adverse effects are less.

Sleep Apnea is a major sleep disorder which leads to a partial or complete stopping in breathing for a short duration of time during sleep. The out-turn of this is extreme daytime drowsiness. Among different polysomnographic signals, Electroencephalogram (EEG) signal reflects the electrical activity of the brain by sensing and recording the brain's activities. Thus, EEG serves as a valuable information source for detecting the sleep apnea events. In this research, an efficient automatic method is proposed for differentiating apnea and non-apnea events of an apnea patient which is a very burdensome task if performed manually. The features energy, entropy, mean absolute deviation and kurtosis, extracted from five sub-bands, provide better accuracy, sensitivity and specificity as compared to other recently published studies. The performance evaluation of the proposed technique is carried out using the publicly available Physionet dataset. The highest classification accuracy of 95.10%, sensitivity of 93.20% and specificity of 96.80% is achieved by using Ensemble decision tree methods using the bagging technique. The novel method proposed in this research offers superior results in terms of accuracy, sensitivity and specificity as compared to the recently published work on the same database.

Colorectal cancer is a life-threatening and therapeutically challenging disease. Increasingly it is being deciphered that genetic and epigenetic mutations play a central role in cancer onset and progression. Excitingly, discovery of non-coding RNAs is considered to be a milestone in molecular oncology and emerging evidence is deepening our understanding about pivotal role of miRNAs in carcinogenesis. miR-143 has been experimentally verified to play an instrumental role as tumor suppressor. Recent studies suggest that single nucleotide polymorphisms rs41291957 and rs353292 in miR-143 may associate with the progression and or development of colorectal cancer. In present study 400 Pakistani subjects participated including 200 colorectal cancer patients and 200 age and gender matched healthy individuals. Blood samples and clinical information of the confirmed patients was collected from cancer diagnosis and treatment hospitals in Pakistan. The polymorphisms rs41291957 and rs353292 were genotyped in patients and controls by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and results were validated by Sanger sequencing. The association of the SNPs within the study group was analyzed by χ² test with p value < 0.05 as significant. Odds ratio was calculated with 95% confidence interval.Genetic predisposition to cancer was observed in presence of characteristic rs45291957 polymorphism. χ² test results show strongly significant association mi-RNA rs45291957 SNP with colorectal cancer p value 0.0111 (

Introduction The impact of direct-acting antiviral agents (DAAs) on the development of hepatocellular carcinoma (HCC) is controversial and a part of the scientific community believes it as a biased interpretation of data. Many studies have reported an aggressive pattern of HCC after DAA use. In this study, we attempted to assess the changes in the pattern of HCC after treatment with DAAs or PI (PEG, pegylated-interferon). Methods A total of 37 HCC patients after DAA treatment and 21 HCC patients after PI treatment were included. The diagnosis of HCC was made and information about demographics, HCC infiltrative pattern, portal vein thrombosis (PVT), time at initial presentation, Child-Turcotte-Pugh (CTP) score, and Barcelona Clinic Liver Cancer (BCLC) stage were compared in the two groups. Results The total number of male patients in the DAA group was 62% while either gender was almost equal in PI. The age group of 40-60 was more prevalent in the DAA group while the PI group comprised more patients who were above 60 years. Patients in the DAA group presented after 3.35 years on average while patients in the PI group presented after about seven years. Most of the patients presented with the CTP stage of A. That is true for both groups. For BCLC staging, most of the patients had stage C, which means multiple lesions. At the initial presentation, most of the patients presented with multifocal lesions. Conclusion Our study found no significant difference in the initial presentation between both groups. However, HCC patients with prior DAA therapy presented early than those with PI therapy.

Distal renal tubular acidosis (RTA) is characterized by inability to secrete hydrogen irons from the distal tubule...

Pneumothorax is a frequent, life-threatening complication, specifically in critically ill patients...

Background Migraine is amongst the top 10 most disabling conditions, and the disease burden is highest in young and middle-aged women. Another variant of the migraine headache, menstrual migraine (MM) is experienced by this cohort of patients. Former studies have done comparisons between various demographic and clinical features of MM versus menstrual-unrelated migraine (MUM) in patients presenting to various clinics with the primary complaint of headaches. We aimed to compare symptoms of migraine in women attending gynecology outpatient clinics, regardless of their presenting complaint. This would help lessen the selection bias and produce more generalizable results. Methods and materials A cross-sectional study was conducted in the outpatient gynecology clinics at a tertiary care hospital over six months. The clinic attendees were screened for sufferers of a primary headache of the migraine type. The migraineurs were then stratified into groups A, MM patients, and group B, MUM patients, using the International Headache Society (HIS) criteria. They were then questioned for the presence of various symptoms associated with their migraine attacks for comparison. Results One-hundred eighty-one women (between 12 years to 55 years) were found to have primary headaches; amongst these, 126 patients met the inclusion criteria and consented to participate; from these, 62 (49.2%) patients had MM and 64 (50.8%) patients had MUM. The symptoms of nausea (p=0.00269), photophobia (p=0.000088), and phonophobia (p=0.0281) were statistically higher in MM patients while vomiting was not a significant feature. Both groups had a predominantly unilateral headache. The average days of the attack had a significant difference between the two groups (p=0.000019), where the duration was longer for MM patients. Conclusions It was observed that patients with MM tend to experience more features associated with migraine headaches, including a longer duration of attacks, and have a worse experience overall.

In obstructive sleep apnea (OSA), there are brief episodes of partial or total upper airway obstruction during sleep, which leads to apnea or hypopneas. Much attention is required to understand OSA's effects on the human body, owing to how common but under-diagnosed this disorder remains. Though the role of OSA in cardiovascular (CV) disease is commonly discussed, it remains unclear how it induces changes in the human body. The intermittent and recurrent hypoxia occurring at the cellular level in this condition is critical for the dramatic changes observed. Vascular endothelial cell (VEC) injury and other mechanisms seen in OSA lead to changes in the CV system. OSA can take a toll on a person's overall functioning, especially with so much importance in today's time on preventing and treating cardiac-related deaths. A total of 31 published articles were included from the PubMed database for our literature review. Most of the studies showed a strong association of OSA with hypertension, especially resistant hypertension. Findings were consistent with OSA's independent role in causing CV diseases, included heart failure, coronary artery disease (cardiac ischemia), arrhythmias, and ischemic stroke. Continuous Positive Airway Pressure (CPAP) is one of the reliable and beneficial treatments for OSA patients. OSA is a treatable and modifiable risk factor for cardiac events and related deaths. The primary purpose of our review article was to address any existing gaps between OSA and its effect on the human body with particular emphasis on cardiovascular changes.

Pituitary stalk interruption syndrome (PSIS) is a rare, congenital disorder characterized by a triad of a thin or interrupted pituitary stalk, aplasia or hypoplasia of the anterior pituitary, and absent or ectopic posterior pituitary (EPP) seen on magnetic resonance imaging (MRI). It can either present at birth or later in life. PSIS is very heterogeneous with respect to its hormonal, clinical, and radiological presentation. The patient described is an 18-year-old male who presented with complaints of short stature and underdeveloped secondary sexual characteristics with weight and height of less than three percentiles for his age. The secondary sexual characteristics were consistent with Tanner Stage II. Some of the pituitary hormones were also deficient. Wrist X-ray was compatible with a bone age of a seven- to eight-year-old. MRI confirmed the diagnosis of PSIS (pituitary stalk interruption syndrome).

This study aims to review the evidence regarding the association between peripheral artery disease (PAD) and rheumatoid arthritis (RA), as well as influential underlying factors and diagnostic options. Eligible literature was searched in PubMed published up to June 1, 2020, in English. Case studies, case series, reviews, and meta-analyses were excluded. We also excluded non-human studies and those 20 years and older. A total of 44 studies were finally incorporated in the narrative review. The results indicated that compared to controls, RA patients are more prone to PAD. Traditional risk factors, disease-characteristics, vitamin D deficiency, therapy used, and other relevant conditions have a variable effect on overall PAD progression. Studies comparing diagnostic options revealed that vascular function and morphology are connected but are still distinctive processes. In early-stage disease, there are functional alterations in the endothelium that can be controlled by anti-inflammatory medications. Ankle-Brachial Index (ABI)

The mainstay of treatment for type 1 diabetes is insulin. The use of insulin for tight glycemic control is the key to preventing micro- and macrovascular complications, but it can also lead to hypoglycemic episodes. Therefore, there is a need for the introduction of a drug that can maintain glucose levels within a safe range without increasing the risk of hypoglycemia. For this reason, SGLT2 (sodium-glucose co-transporter-2) inhibitors has been a hot topic in the last couple of years. They have been proved very efficient in treating type 2 diabetes. Many trials on the safety and efficacy of SGLT2 inhibitors have been done on type 1 diabetics. Some other studies have also been done that prove their benefits in increasing arterial efficacy and reducing GFR (glomerular filtration rate). This review article discusses the benefits and risks. The literature search was performed using PubMed, and after applying the inclusion and exclusion criteria, 16 published papers were found. All relevant articles on the topic have been included. Our review has shown that the benefits of SGLT2 inhibitors outweigh their risks. Their benefits include good glycemic control, HBA1c (glycated haemoglobin) reduction, weight loss, and blood pressure improvement. Furthermore, improvement in GFR and arterial efficacy is also significant. Side effects such as UTI (urinary tract infection) and genital infection have been observed, but their incidence is low. However, DKA (diabetic ketoacidosis) and hypoglycemia are severe side effects that should be highlighted. Hypoglycemia can be prevented by strictly monitoring blood sugar levels. The patient must be educated and counseled about DKA and its symptoms. This will ensure the safety of the patient as euglycemic DKA can prove fatal if not diagnosed earlier. So, SGLT2 inhibitors can be used as an effective drug to control blood sugar levels in type 1 diabetes, especially in patients with a BMI higher than 30. It will not only achieve the treatment goals but can also decrease the morbidity and mortality of the patients. However, more studies need to be done to fully understand DKA caused by SGLT2 inhibitors.

The measurement of biological processes at a molecular and cellular level serves as a basis for molecular imaging. As compared with traditional imaging approaches, molecular imaging functions to probe molecular anomalies that are the basis of a disease rather than the evaluation of end results of these molecular changes. Proteases play central role in tumor invasion, angiogenesis and metastasis thus can be exploited as a target for imaging probes in early diagnosis and treatment of tumors. Molecular imaging of protease has undergone tremendous breakthroughs in the field of diagnosis. It allows the clinicians not only to see the tumor location but also provides an insight into the expression and activity of different types of markers associated with the tumor microenvironment. These imaging techniques are expected to have a huge impact on early cancer detection and personalized cancer treatment. Effective development of protease imaging probes with the highest in vivo biocompatibility, stability and most appropriate pharmacokinetics for clinical translation will upsurge the success level of early cancer detection and treatment.

Single Nucleotide Polymorphisms (SNPs) are the most common candidate mutations in human beings that play a vital role in the genetic basis of certain diseases. Previous studies revealed that Solute Carrier Family 26 Member 4 (SLC26A4) being an essential gene of the multi-faceted transporter family SLC26 facilitates reflexive movement of Iodide into follicular lumen through apical membrane of thyrocyte. SLC26A4 gene encodes Pendred protein, a membrane glycoprotein, highly hydrophobic in nature, present at the apical membrane of thyrocyte functioning as transporter of iodide for thyroid cells. A minor genetic variation in SLC26A4 can cause Pendred syndrome, a syndrome associated with thyroid glands and deafness. In this study, we performed in-silico analysis of 674 missense SNPs of SLC26A4 using different computational platforms. The bunch of tools including SNPNEXUS, SNAP-2, PhD-SNP, SNPs&GO, I-Mutant, ConSurf, and ModPred were used to predict 23 highly confident damaging and disease causing nsSNPs (G209V, G197R, L458P, S427P, Q101P, W472R, N392Y, V359E, R409C, Q235R, R409P, G139V, G497S, H723R, D87G, Y127H, F667C, G334A, G95R, S427C, R291W, Q383H and E384G) that could potentially alter the SLC26A4 gene. Moreover, protein structure prediction, protein-ligand docking and Molecular Dynamics simulation were performed to confirm the impact of two evident alterations (Y127H and G334A) on the protein structure and function.

Breast cancer (BC) is the foremost cause of cancer related deaths in women globally. Currently there is a scarcity of reliable biomarkers for its early stage diagnosis and theranostics monitoring. Altered DNA methylation patterns leading to the silencing of tumor suppressor genes are considered as an important mechanism underlying tumor development and progression in various cancer types, including BC. Very recently, epigenetic silencing of SHISA3, an antagonist of β-catenin, has been reported in various types of tumor. However, the role of SHISA3 in BC has not been investigated yet. Therefore, we aimed at evaluating the contribution of SHISA3 in BC causation by analyzing its expression and methylation levels in BC cell lines (MDA-MB231, MCF-7 and BT-474) and in 103 paired BC tissue samples. The SHISA3 expression and methylation status was determined by qPCR and methylation specific PCR (MSP) respectively. The role of SHISA3 in BC tumorigenesis was evaluated by proliferation and migration assays after ectopic expression of SHISA3. The association between SHISA3 hypermethylation and clinicopathological parameters of BC patients was also studied. The downregulation of SHISA3 expression was found in three BC cell lines used and in all BC tissue samples. However, SHISA3 promoter region was hypermethylated in 61% (63/103) tumorous tissues in comparison to the 18% of their matched normal tissues. The 5-aza-2'-deoxycytidine treatment restored SHISA3 expression by reversing promoter hypermethylation in both MDA-MB231 and MCF-7 cells. Furthermore, ectopic expression of SHISA3 significantly reduced the proliferation and migration ability of these cells. Taken together, our findings for the first time reveal epigenetic silencing and tumor suppressing role of SHISA3 in BC. Henceforth, this study has identified SHISA3 as potentially powerful target for the development of new therapies against BC, as well as novel diagnostic and therapy response monitoring approaches.

Adolescent pregnancies are a global health problem with over 16 million children born to this age group globally. Adolescent females also represent almost half of all adolescent global migrants. Adolescent pregnancy by itself is associated with poor health care access and morbidities; the additional risk of social insecurity in the case of undocumented adolescent migrants leads to higher risks for the mother and newborn. According to the CDC, adolescents comprise half of all new sexually transmitted diseases (STDs) including reported primary and secondary syphilis. Our case highlights the relationship between social insecurity for the undocumented adolescent migrant and excess risks for preventable mother-to-child transmission of communicable diseases. In formulating preventive measures and policies for the recent rise in sexually transmitted maternal diseases with resultant congenital infections, there is need for health care systems and providers to familiarize themselves with advocacy and other useful resources that will promote health care access for undocumented and other vulnerable adolescents. Additionally, local providers who work in areas with a large population of immigrant adolescents should utilize the untapped resources of these adolescents to develop youth community advocacy projects that link adolescents to health resources, including reproductive health.

Obesity is an abnormal condition in which excessive fat is accumulated in adipose tissue. It has emerged as one of the biggest public health concerns today as it is a major risk factor for developing type 2 diabetes, cardiovascular disease, hypertension, and certain types of cancer. Carotenoids play a key role in maintaining health and preventing diseases because of their remarkable structural and physical properties involving antioxidant, antiinflammatory, and anticancer activities, which render them a remarkable position in the amelioration of various metabolic syndromes. In vitro and in vivo as well as human-interventional studies dealing with carotenoids shed light on the targets of major regulatory mechanisms of adipogenesis and pathophysiology concerning obesity and related metabolic disorders. This chapter primarily focuses on the antiobese molecular mechanisms of carotenoids particularly targeting adipocyte differentiation, thermogenesis, inflammation, and lipogenesis in view toward the management of obesity.

There is much evidence that diabetes mellitus (DM)-induced hyperglycemia (HG) is responsible for kidney failure or nephropathy leading to cardiovascular complications. Cellular and molecular mechanism(s) whereby DM can damage the kidney is still not fully understood. This study investigated the effect of streptozotocin (STZ)-induced diabetes (T1DM) on the structure and associated molecular alterations of the isolated rat left kidney following 2 and 4 months of the disorder compared to the respective age-matched controls. The results revealed hypertrophy and general disorganized architecture of the kidney characterized by expansion in glomerular borders, tubular atrophy and increased vacuolization of renal tubular epithelial cells in the diabetic groups compared to controls. Electron microscopic analysis revealed ultrastructural alterations in the left kidney highlighted by an increase in glomerular basement membrane width. In addition, increased caspase-3 immunoreactivity was observed in the kidney of T1DM animals compared to age-matched controls. These structural changes were associated with elevated extracellular matrix (ECM) deposition and consequently, altered gene expression profile of ECM key components, together with elevated levels of key mediators (MMP9, integrin 5α, TIMP4, CTGF, vimentin) and reduced expressions of Cx43 and MMP2 of the ECM. Marked hypertrophy of the kidney was highlighted by increased atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) gene expression. These changes also correlated with increased TGFβ1 activity, gene expression in the left kidney and elevated active TGFβ1 in the plasma of T1DM rats compared to control. The results clearly demonstrated that TIDM could elicit severe structural changes and alteration in biochemical markers (remodelling) in the kidney leading to diabetic nephropathy (DN).

Objectives This study was conducted to determine if thalassemia patients were getting quality care in Rawalpindi and Islamabad, Pakistan, as per international standards and to identify determinants for better quality of thalassemia care. Design A cross sectional study was conducted using interview based structured questionnaire, which was developed using standards of thalassemia care used by International Thalassemia Foundation. Setting Five healthcare facilities catering to the needs of thalassemia patients in Rawalpindi and Islamabad, Pakistan. Participants Data were collected from 315 thalassemia patients from May to August, 2016. Main outcome measure Survey data on quality indicators. Results Results showed that almost half of thalassemia patients (48.5%) were getting poor quality of care. On average patients were getting only 63.93% of possible quality care for the disease. The most deficient quality area was management of complications where patients were getting only 49.1% of possible care. Better quality of care was likely to be received by those patients who were educated, patients with educated fathers, those visiting private facilities and those who were visiting facilities in Islamabad. Those with concomitant diseases were also likely to receive better care. Conclusion Quality of care provided to thalassemia patients was well below the international standards for the care of thalassemia. There is a need to take urgent action to improve quality of care in the country.

Polycystic ovarian syndrome (PCOS), a common endocrinal disorder of reproductive age characterized by heterogeneous complications, is nowadays prevailing among females at adolescent stage. Infrequent or prolonged menstrual periods, excess hair growth, acne, and obesity can occur in women with PCOS. In adolescents, infrequent or absence of menstruation may raise chances for this condition. The increased prevalence of PCOS among general population throughout the world is found to be 5%-10% in the women of reproductive age, and about 40% women with PCOS experience depression, particularly young girls. The exact cause of PCOS is unknown. Early diagnosis and treatment along with weight loss may reduce the risk of long-term complications. Depression and anxiety are common in women with PCOS but are often overlooked and therefore left untreated. Along with the physical disturbances, many mental problems are also associated with PCOS. Therefore, PCOS not only has problems associated with reproduction but also has associated crucial metabolic and psychological health risks with increasing age of the patients. Because of the increased number of cases with PCOS around the world in present times, with prominent symptom of, specifically, depression at the adolescent stage, it is important to highlight the disease.

Chronic hepatitis B is a worldwide health problem. Hepatitis D virus (HDV) is a dependent virus that relies on hepatitis B virus (HBV) to synthesize the pathogenic genomes. This may lead to HDV and HBV coinfection or superinfection that results in rapid liver damage that may lead to various serious complications, such as acute liver failure, cirrhosis, and hepatocellular cancer requiring liver transplantation. However, post-transplant HBV reactivation is always a concern as it can be detrimental to allograft function, leading to poor survival. The mainstay strategy to prevent this has been prophylaxis with hepatitis B immunoglobulin (HBIG) and potent anti-viral drugs. This treatment option has been investigated over the years in terms of appropriate dosing, duration and combination. Furthermore, with the advent of more potent antivirals there have been suggestions to use them as a monotherapy. Although, currently there is no effective therapy available for HDV, but the success of the liver transplantation in these patients is dependent on preventing HBV recurrence. Therefore, there has been a continuous effort to come up with an effective treatment plan that is effective and economical. In this review, we discuss the available treatment options for HBV/HDV after liver transplantation.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide and liver transplantation (LT) is the only potentially curative treatment. Over the years, Milan criteria has been used for patient selection. There is ongoing research in this field with introduction of new biomarkers for HCC that can help guide future treatment. Furthermore, newer therapies for downstaging of the tumor are being implemented to prevent dropout from the transplant list. In addition, combination therapies for better outcome are under investigation. Interestingly, the concept of living-donor LT and possible use of hepatitis C virus-positive donors has been implemented as an attempt to expand the organ pool. However, there is a conflict of opinion between different centers regarding its efficacy and data is scarce. The aim of this review article is to outline the various selection criteria for LT, discuss the outcomes of LT in HCC patients, and explore future directions of LT for HCC. Therefore, a comprehensive PubMed/MEDLINE review was conducted. To expand our search, references of the retrieved articles were also screened for additional data. After selecting the studies, the authors independently reviewed them to identify the relevant studies. After careful evaluation 120 studies relevant to out topic are cited in the manuscript. Three tables and two figures are also included. In conclusion LT for HCC has evolved over the years. With the introduction of several expanded criteria beyond Milan, the introduction of bridging therapies, such as transcatheter arterial chemoembolization and radiofrequency ablation, and the approval of newer systemic therapies, it is evident that there will be more LT recipients in the future. It is promising to see ongoing trials and the continuous evolution of protocols. Prospective studies are needed to guide the development of a pre-LT criteria that can ensure low HCC recurrence risk and is not overly stringent, clarify the role of LDLT, and determine the optimal bridging therapies to LT.

Background Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG) is an unexplored therapy amidst the rapidly evolving spectrum of medical therapies for COVID-19 and is expected to counter the three most life-threatening consequences of COVID-19 including lung injury by the virus, cytokine storm and sepsis. Methods A single center, phase I/II, randomized controlled, single-blinded trial was conducted at Dow University of Health Sciences, Karachi, Pakistan. Participants were COVID-19 infected individuals, classified as either severely or critically ill with Acute Respiratory Distress Syndrome (ARDS). Participants were randomized through parallel-group design with sequential assignment in a 4:1 allocation to either intervention group with four C-IVIG dosage arms (0.15, 0.20, 0.25, 0.30 g/kg), or control group receiving standard of care only (n = 10). Primary outcomes were 28-day mortality, patient's clinical status on ordinal scale and Horowitz index (HI), and were analysed in all randomized participants that completed the follow-up period (intention-to-treat population). The trial was registered at clinicaltrials.gov (NCT04521309). Findings Fifty participants were enrolled in the study from June 19, 2020 to February 3, 2021 with a mean age of 56.54±13.2 years of which 22 patients (44%) had severe and 28 patients (56%) had critical COVID-19. Mortality occurred in ten of 40 participants (25%) in intervention group compared to six of ten (60%) in control group, with relative risk reduction in intervention arm I (RR, 0.333; 95% CI, 0.087–1.272), arm II (RR, 0.5; 95% CI, 0.171–1.463), arm III (RR, 0.167; 95% CI, 0.024–1.145), and arm IV (RR, 0.667; 95% CI, 0.268–1.660). In intervention group, median HI significantly improved to 359 mmHg [interquartile range (IQR) 127–400, P = 0.009)] by outcome day, while the clinical status of intervention group also improved as compared to control group, with around 15 patients (37.5%) being discharged by 7th day with complete recovery. Additionally, resolution of chest X-rays and restoration of biomarkers to normal levels were also seen in intervention groups. No drug-related adverse events were reported during the study. Interpretation Administration of C-IVIG in severe and critical COVID-19 patients was safe, increased the chance of survival and reduced the risk of disease progression. Funding Higher Education Commission (HEC), Pakistan (Ref no. 20-RRG-134/RGM/R&D/HEC/2020).

Lung cancer is fatal and spreading rapidly worldwide. Different clinical strategies are applied to stop this cancer. As the lung is a delicate organ, special clinical applications must be used and nanodrugs delivery systems are the most important applications of all. This review discusses the lung problems such as lung cancer, lung inflammation and bronchi constrictions followed by repetitive intake of some drugs. The objective of this review is to study how nanodrug delivery systems were synthesized and used in lung disorder treatment especially in lung cancer. The authors studied some articles from 1989 to 2015. Liposome encapsulation was done in various ways for the delivery of different drugs such as metaproterenol into liposomes caused bronchodilation, immunoliposomes bearing antibodies for doxorubicin reduced 50% inhibitory effects, radioliposomes with high penetrating ability to peripheral airways, aerosol delivery systems with deep pulmonary deposition, polymeric drug delivery having potential to improve beneficial index of drug, solid lipid liposomes, liposomal gentamicin with altered different clinical susceptibilities of resistance, transferrin conjugated liposomes to deliver cytostatic drugs to site of lungs, anti-inflammatory drugs with mannosylated liposomes, liposomal suspensions with single stranded RNAs and peptide encapsulation of liposomes. This review indicates that many animals perished with intravenous administration of drugs but survived in liposomal targeting groups.

Introduction2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance.MethodsThis was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009–2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence).ResultsOf 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60–1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14–2.28) when Hr genotype was included, but this analysis lacked power (p=0.42).ConclusionsIn a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations.

Background: Hepatitis C is a serious disease caused by infection of HCV virus. This virus mainly infects hepatocytes but it also replicates in the other tissues of human body, causing different types of extrahepatic manifestations.Methods: We conducted a case-control study from March 2014 to June 2014, to investigate frequency of skin diseases among 75 HCV infected patients and 75 controls identified in NOORI hospital, Islamabad Pakistan. We also investigated the association of skin diseases with HCV infection. Case patients were confirmed symptomatic cases of hepatitis C infection with laboratory and clinical criteria meeting standards provided by CDC. Controls were selected as the people without HCV, HBV, HIV and other chronic diseases. Data regarding sociodemographic characteristics, clinical data and skin diseases was collected using structured performa. Chi square test was used to see association.Results: The prevalence of skin diseases in cases were 33.3% (25/75). Most common skin diseases among HCV patients was Pruritus (32%) followed by Psoriasis (12%). Case-patients were more likely than controls to have skin diseases (OR=4.85, CI 1.95-12.12).Conclusion: Our study indicates high prevalence of skin diseases in HCV infected patients. It also showed clear association of skin diseases with HCV infection. We recommend studies on large scale to have a better look on these skin complications and use of these Skin diseases as prognostic indication of HCV infection.

This study was aimed at presenting a continuous and spatially coherent picture of ammonia (NH3) distribution over the Indo-Gangetic Plain (IGP) by exploiting satellite observations. Atmospheric columns of ammonia were mapped over South Asia by using TES observations on board NASA’s Aura satellite. Monthly mean data were used to identify emission sources of atmospheric ammonia across the South Asian region. Data were analysed to explore temporal trends, seasonal cycles, and hot spots of atmospheric ammonia within the study area. The results show that the IGP region has the most ammonia concentrations in terms of column densities, and hence this region has been identified as an ammonia hot spot. This is attributed majorly to extensive agricultural activity. Time series showed a slight increase in ammonia column densities over the study area from 2004 to 2011. Different seasonal cycles were identified across the IGP region with maximum NH3 columns observed during the month of July in most of the subregions. Seasonality in an ammonia column is driven by different cropping patterns and meteorological conditions in the IGP subregions. Global emission inventories of atmospheric ammonia were largely overestimating as compared to satellite observations.

BACKGROUND: Dementia is a common form of Alzheimer disease which is affecting the quality of older adults’ life. Non-drug treatment such as cognitive therapies are more beneficial for such patients. These days, mobile applications are providing tremendous opportunities for aiding the medicinal treatment.OBJECTIVES: This paper presents CareD – a mobile application based solution for dementia patients and their caregivers. Unlike, other available mobile applications, CareD provide a single resolution for maximum dementia related complications. The main objective of this application is to improve the quality of life of dementia patients and facilitate their caregivers. CareD also aims at providing native language support i.e. Urdu to the people of Pakistan. METHODS: CareD comprises of various modules including cognitive therapy sessions, patient tracking, reminders, healthy living to aid dementia patients in their everyday activities. Experimental study involving dementia patients and their caregivers has been carried out to evaluate the usability and effectiveness of this application. RESULTS: Twenty patients were included in the study. Results showed that CareD is very effective and helpful in decreasing the disease progression as well as in relieving the burden of caregivers. CONCLUSION: CareD has been found to be a useful and efficient solution for dementia patients. It was observed that utilization of mobile application was progressively successful in reducing the stress of both; patients and their caregivers. The use of native language Urdu made the application more learnable for older adults and improved its acceptance.

As a novel biomarker from the STEAP family, STEAP2 encodes six transmembrane epithelial antigens to prostate cancer. The overexpression of STEAP2 is predicted as the second most common cancer in the world that is responsible for male cancer-related deaths. Nonsynonymous SNPs are important group of SNPs which lead to alternations in encoded polypeptides. Changes in the amino acid sequence of gene products can lead to abnormal tissue function. The present study firstly sorted out those SNPs which exist in the coding region of STEAP2 and evaluated their impact through computational tools. Secondly, the three-dimensional structure of STEAP2 was formed through I-TASSER and validated by different software. Genomic data has been retrieved from the 1000 Genome project and Ensembl and subsequently analysed using computational tools. Out of 177 non-synonymous single nucleotide polymorphisms (nsSNPs) within the coding region, 42 mis-sense SNPs have been predicted as deleterious by all analyses. Our research shows a welldesigned computational methodology to inspect the prostate cancer associated nsSNPs. It can be concluded that these nsSNPs can play their role in the up-regulation of STEAP2 which further leads to progression of prostate cancer. It can benefit scientists in the handling of cancerassociated diseases related to STEAP2 through developing novel drug therapies.