Thursday, 28 December 2017

Which Criteria to use for the Diagnosis of Behcet’s Disease: International Study Group (ISG) Criteria or International Criteria for Behcet’s Disease (ICBD)?

It is interesting to note that Behcet’s Disease (BD) is one of those diseases which had an early diagnostic criteria (9 years after its official recognition, with the Curth criteria in 1946), having one of the largest number of classification/diagnosis criteria (17 sets, in 70 years, till 2016), among them only 2 real International Criteria (ISG and ICBD), and having one of the largest international participation (27 countries for ICBD). The ISG criteria were created by the collaboration of 7 countries (France, Iran, Japan, Tunisia, Turkey, UK, and USA) in 1990. The ICBD was first presented in 2006 to the International Conference on Behcet’s Disease in Portugal and the revised version in 2010 to the International Conference on Behcet’s Disease in London, and published in 2014.
The sensitivity of ISG criteria was very good, at 92%, when checked on the patients gathered from the 7 countries. The specificity was excellent at 97%. Originally, the accuracy was not checked and instead the relative value, which was 189 (the sum of sensitivity and specificity). When the performance of the criteria was checked, for validation, in different countries, the sensitivity was low, while the specificity was high. The problem came from two main biases. First, as the majority of BD patients gathered from the seven countries had oral aphthosis (OA), this manifestation was put as a mandatory symptom to be present for diagnosis, while all over the world, when patients are diagnosed by expert opinion, around 5% of patients diagnosed as having BD miss OA. Second, the patients’ selection: overall 886 BD patients and 97 control patients were selected from the seven collaborating countries, with 366 (41.3%) from Iran, 285 (32.2%) from Turkey, and 141 (16.9%) from Japan, which made 90.4% from 3 countries and less than 10% of the remaining 4 countries. From Western countries, only 5% had BD. To be classified as having BD, a patient must have oral aphthosis (mandatory), and two of he following manifestations: genital aphthosis, skin manifestations (pseudo-folliculitis, erythema nodosum), ophthalmologic manifestations (anterior uveitis, posterior uveitis, retinal vasculitis), positive pathergy test.
For ICBD, patients were gathered from 27 countries, all over the world. This time, it was paid enough attention to not make the same error in the patient selection, and to have enough patients from the Western world. A total of 2556 BD and 1163 controls were gathered, with 35.1% from 9 countries of the Western world. The revised ICBD performance in the cohort of the international patients was: sensitivity 96%, specificity 91.2%, and accuracy 94.5%. ICBD was validated in Germany, China, Iran, and Italy. The revised ICBD was validated in Iran  with sensitivity 96.8% (ISG 78.1%), specificity 97.2% (ISG 98.8%), and accuracy 97% (ISG 85.5%). To be classified as having BD, a patient must get 4 points from the ICBD. Oral aphthosis, genital aphthosis, and ophthalmologic manifestations (anterior uveitis, posterior uveitis, retinal vasculitis) get each 2 points. Skin manifestations (paseudo-folliculitis, erythema nodosum, skin aphthosis), vascular manifestations, neurological manifestations, and positive pathergy test get each one point.

Wednesday, 27 December 2017

Vitrified-Warmed Blastocyst Score Effects Pregnancy Outcomes: Towards a Single Blastocyst Vitrification and Transfer

No a referable quality selection criteria for a single vitrified-warmed blastocyst transfer. Therefore, the present study aimed to investigate the relationship between vitrified-warmed blastocyst score and clinical pregnancy outcomes. This retrospective analysis consisted of 221 patients undergoing two blastocysts transfer on thawing day. Implantation rate, fetal heart pregnancy rate, live-birth rate, multiple birth rate were analyzed. When a patient received two high-quality vitrified-warmed blastocysts (=3BB), implantation rate and fetal heart pregnancy rate were 48.2% and 65.5%, respectively. The multiple birth rates in this group were 44.4%. When two vitrified-warmed blastocysts (one =3BB and another <3BB) were available for transfer, implantation rate and fetal heart pregnancy rate were 34.5% and 52.7%. The multiple birth rate for this group was 29.6%. When only two generalquality vitrified-warmed blastocysts (<3BB) were transferred, implantation rate and fetal heart pregnancy rate were 21.7% and 35.9%, and the multiple birth rate was 21.7%.
The ability to transfer one good-quality vitrified-warmed blastocyst (=3BB) should lead to fetal heart pregnancy rates greater than 52% and live birth rates greater than 36%. Results of the present study can provide guidelines for a single vitrified-warmed blastocyst transfer, which is an effective means of eliminating multiple gestations and avoiding the complications associated with such pregnancies. Multiple pregnancies are a complication of human Assisted Reproductive Technology (ART), rather than a successful result. So, how to reduce the multiple pregnancy rates and maintain the acceptable overall live-birth rate have become research hotspots in the area of reproductive medicine. The strategy of a single embryo transfer is the most effective way to achieve single pregnancy.
Transfer of an embryo with a high potential for development and implantation is a key success factor in ART. Routine blastocyst culture using sequential culture media in vitro can make a better assessment for embryo viability and may confer a selection advantage. Moreover, blastocyst transfer has been associated with a higher implantation rate and a better synchronization between endometrial receptivity and embryo. In a conventional In Vitro Fertilization (IVF) cycle, the use of exogenous gonadotropins results in Ovarian Hyper Stimulation Syndrome (OHSS). Cryopreservation programs are essential for patients who suffered from OHSS. Moreover, for infertile women with the polycystic ovary syndrome, frozen-embryo transfer was associated with a higher rate of live birth and a lower risk of the OHSS than fresh-embryo transfer after the first transfer, because vitrified- warmed blastocyst transfer occurs within a uterine environment that more closely resembles spontaneous conception. In addition, cryopreservation process is used for the storage of supernumery embryos to increase cumulative pregnancy rate.

Tuesday, 26 December 2017

The Epidemiology of Variola Major

Good studies of the epidemiology of smallpox (Variola major) were conducted in Asia, Africa, and Europe in the late 1960’s and early 1970’s. These studies showed that transmission is fairly slow and generally to susceptible persons who had prolonged face-to-face contact with patients, often as caregivers. Patients are not infectious during the violent prostrating prodrome caused by intense viremia. The rare exceptions to this pattern include true airborne spread, and spread by aerosols created by shaking out heavily infected bedding.Vaccination of contacts within two or three days after exposure generally protects them and aborts the disease. Thus contacts must be identified quickly and vaccinated with good vaccine and vigorous technique.
These epidemiologic facts led to the development of the surveillance and containment methodology, which became the main tool for the eradication program. This consisted of active search for patients, effective patient isolation, identification of their close contacts, vaccination of contacts, supervision of the contacts to immediately isolate them if they developed a fever, and if time and staff permitted identification of the contacts of contacts, the “second ring”. In the unlikely occurrence of a bioterrorist attack employing smallpox, surveillance and containment methods should be the mainstay of control efforts.
In the late 1960’s, the Smallpox Eradication Program switched from a strategy of mass vaccination to intensive surveillance and containment of outbreaks. This change brought about rapid success of the eradication program. The switch was based on studies of the epidemiology of smallpox in West Africa, India, East and West Pakistan, Bangladesh  and Europe conducted in the late 1960’s and early 1970’s. These studies showed that Variola major was less infectious than previously believed, that its spread was usually quite limited, and that vaccination of the immediate contacts of patients rapidly eliminated the disease. This paper reviews these findings and discusses our current understanding of the transmission and spread of the disease.

Variola major is spread from person to person by direct, usually prolonged, face to face personal contact, during which a non-immune individual inhales virus particles from the exhalations of the infected patient. There is no animal host of variola virus, and no one can become an asymptomatic carrier. Patients are not infectious during the prodrome despite an intense viremia. Patients become infectious from the appearance of the rash on the skin and the pharynx, usually two or three days after the onset of the prodrome. The soft tissue in the back of throat has no covering like the squamous layer of the skin, so the virus is shed into the nasopharynx before it is shed from the skin lesions. Most spread is generally to bedside care givers, since most virus is carried in large droplet nuclei which rarely travel more than 6 feet from the patient. Most patients can remember being at the bedside of an obviously ill individual.

Friday, 22 December 2017

Yap Regulation of Hepatic Stellate Cells: Is there a Role for Metabolic Stress?s

Mannaerts et al. recently reported that the effect or protein, Yap of the Hippo pathway regulates liver fibrosis by controlling the activation of hepatic stellate cells. The authors elegantly demonstrate that Yap activation induces fibrotic phenotype using in vitro as well as in vivo models. Besides contributing to liver failure, cirrhosis an advanced stage of fibrosis is known to be a major underlying disease of primary liver cancer, Hepatocellular Carcinoma (HCC). Thus experimental characterization of Yap’s role in fibrogenesis is clinically relevant due to the necessity for a viable antifibrotic therapy.

Emerging data show that Yap and hippo pathway in general are involved in liver enlargement and the associated clonal expansion of HCC. Yet, detailed mechanistic insights on the molecular regulation of fibrogenesis by Yap remain unclear. Recent reports document that energy producing pathways are altered in early/late cirrhotic stages and selective deregulation/ disruption of such metabolic alteration block fibrotic phenotype in vitro and in vivo.Thus, accumulating data indicate that metabolic alteration is indispensable for the progression of fibrosis/ cirrhosis. Corroborating this, Yap and Hippo signaling mechanism have also been found to be regulated by energy stress. Importantly, glucose-mediated energy homeostasis has been shown to regulate Hippo pathway which in turn affects pro-glycolytic function of Yap. Multiple lines of evidence have established that metabolism-related oxidative stress is a major facilitator of fibrosis. Intriguingly, evidences also show that Yap- Hippo pathway is affected by oxidative stress. Taken together, it is thus far evident that cellular stress contributes for fibrogenesis and Yap-Hippo pathway is affected by such cellular stress during fibrogenesis. Future investigations focusing on molecular intricacies of Yap regulation by metabolic stress will be critical and relevant to identify potential therapeutic target (s) and development of any viable and translatable strategy to treat liver fibrosis/cirrhosis.

Thursday, 21 December 2017

An Update on the Components and Functions of Bone Marrow Niche

In the embryonic stage, hematopoiesis happens in different anatomical locations; including liver, spleen, yolk sac, aorta-gonadmesonephros, and bone marrow, while the main location for hematopoiesis during the adulthood is the bone marrow. In the bone marrow, a highly supportive microenvironment which is called niche maintains the best conditions for the existence of hematopoietic stem cells (HSCs).
This dynamic microenvironment provides all the cellular components and molecular signals that are essential for HSC maintenance and ensures the rapid blood production for daily needs. Most of our new vision about niche comes from advanced imaging technologies, different transgenic mouse models and in vivo lineage tracing studies.
Through these, researchers are trying to discover the cellular and molecular components of niche. The major cellular constituents of the niche are mesenchymal stem cells (MSCs) and their derivatives including perivascular cells, osteoblasts and adipocytes, and also endothelial cells and Schwann cells.
The cellular constituents of niche produce several soluble factors including growth factors and cytokines providing regulatory signals required for hematopoiesis. These soluble factors include stem cell factor (SCF), transforming growth factor (TGF-β), C-X-C motif chemokine ligand 12 (CXCL12), angiopoietin-1, granulocyte-colony stimulating factor (G-CSF), Wnt ligands, and thrombopoietin (TPO). In the bone marrow microenvironment, two distinct niches have been proposed.
First, the endosteal niche which harbor a minority of HSCs and seemingly keeps the HSCs in a quiescent state, although this issue is still under debate. Second vascular niche that is mainly comprised of cells with MSC characteristics (Nestin+MSCs, CXCL12-abundant reticular (CAR) cells, Leptin receptor+cells) and prepare the predominant site for HSCs localization. Other vascular niche candidates are arterioles enclosed by pericytes and endothelial cells.
In the homeostasis state, niche precisely controls the HSC fate decisions and adjusts a balance between the rate of HSC self-renewal and differentiation. Mobilization and homing of HSCs which are mirror events are important physiological processes and are highly controlled by niche elements. The crucial role of niche is emphasized by the fact that deregulation of the niche function can lead to initiation and development of hematopoietic malignancies [7,8]. In spite of the great advancements in understanding the niche function, there are open questions that need to be answered.

Wednesday, 20 December 2017

Macroscopic Balance Equations for Spatial or Temporal Scales of Porous Media Hydrodynamic Modeling


We focus on the first author’sprevious work addressing macroscopic balance equations developed for different spatial and temporal scales. We elaborate on previous findings so as to orient the reader to fundamental concepts with which the mathematical formulations are developed. The macroscopic balance Partial Differential Equations (PDE’s) are obtained from their microscopic counterparts by volume averaging over a Representative Elementary Volume (REV), considering a non-Brownian motion. The macroscopic quantity of phase/component intensive quantities product, is the premise of two concurrent decomposed macroscopic balance PDE’s of the corresponding extensive quantity. These are concurrently valid at the primary REV order of length and at a significantly smaller secondary length. The hydrodynamic characteristic at the smaller spatial scale was found to always be described by pure hyperbolic PDE’s, the solution of which presents displacement of sharp fronts. Reported field observations of condensed colloidal parcels motion, validate the suggestion of hyperbolic PDE’s describing fluid momentum and components mass balance at the smaller spatial scale. Controlled experiments supplemented by numerical predication can yield the hydrodynamic interrelation between the two adjacent spatial scales.
Further, we focus on the first author past developments concerning dominant macroscopic balance PDE’s of a phase mass and momentum and a component mass following an onset of abrupt pressure change. These account for the primary REV order of length and for evolving temporal scales. Numerical simulations were found to be consistent in excellent agreement with experimental observations. During the second time increment and in view of the aforementioned developments, we presently elaborate on new findings addressing theoretically the efficiency of expansion wave for extracting solute from a saturated matrix. Simulations comparing between pumping using an approximate analytical form based on Darcy’s equation and numerical prediction addressing the emitting of an expansion wave, suggest that the latter extracts by far more solute mass for a spectrum of different porous media.

Application of spatial averaging rules, referring to a REV, leads to the formulation of the macroscopic balance equations addressing phase interactions such as fluids carrying components and a deformable porous matrix. Further elaborations by Sorek et al. Sorek and Ronen  and Sorek et al.  prove that the phases and components macroscopic balance PDE’s can be decomposed into a primary part that refers to the REV length scale and, concurrently, a secondary part valid at a length scale smaller than that of the corresponding REV length. 

Tuesday, 19 December 2017

Key Beliefs Underlying Students’ Behaviour and Decisions towards HIV/AIDS: Implications for Educational Interventions


Education programmes towards HIV/AIDSprevention are still considered important in response to the epidemic. The study sought to determine key beliefs underlying students’ decisions and behavior towards HIV/AIDS. Beliefs are so pervasive that it merits consideration in behavioral interventions, especially among audiences who are exposed daily to its socializing influences in Ghana. This paper reports on the qualitative approach of a mixed method study involving Junior High School students in Obuasi, Ghana. Data was collected from three sets each of boys, girls and mixed groups’ focus groups and teachers’ interviews and analysed using thematic technique. The value-expectancy theory served as theoretical framework explaining individual‘s strength of motivation to strive for a certain goal to the expectations to attain the desired goal and the incentive value of that particular goal. The conclusions posit a preference for the promotion of abstinence and a dislike for condom promotion to curb the HIV incidence despite perceived prevailing sexual activities among students. The motivations towards abstinence was generally explained within value-based and futuristic expectation framework: pleasing God for blessings, pleasing family to gain respect and social approval, keeping virginity, avoiding negative consequence, and pursuing education for better future and marriage. The findings suggest, values may represent important protective factor: adolescents who strongly identify with such position may less likely engage in HIV risk-related behaviors. A threat to comprehensive HIV education was however, observed due to lack of self-efficacy and apathy towards sex and condoms education influenced significantly by respondent’ beliefs and sensitivity to cultural issues.
 Major advances have been made in almost every area of the HIV epidemic response. However, progress for adolescents is falling behind becoming the leading cause of their death in Africa. Deaths are declining in all age groups, except among 10–19 year olds where new HIV infections are not declining as quickly as among others. Adolescent girls, particularly in sub-Saharan Africa, are most affected. In 2013, more than 860 girls in South Africa became infected every week, compared to 170 boys.

Ghana’s epidemic, described as generalised according to WHO classification, has been on a downward trend with national HIV prevalence from 3.6% in 2003, 2.7% in 2005 to 1.9% in 2007  and 1.47% in 2014 [3]. Despite low national incidence, many “hotspots” record high prevalence of infection. Six out of the ten regions exceed 2.1% (Eastern: 3.7%; Greater Accra: 3.1%; Ashanti: 2.8%). In the 15-24 age groups, the rural areas recorded 1.1% whilst the urban areas recorded 2.4% among pregnant women. A total of 1,889 new child infections (17% of all new infections) were estimated to have occurred among children 0-14 years. The 15-24 year group accounted for 2,901 of the new infections (26% of new infections), of whom 64% were female. An estimated 250,232 persons with 21,223 children (8%) are living with HIV; 11,356 new infections and 9,248 AIDS-related deaths recorded in 2014. Annual AIDS death among children between 0-14 years is estimated at 1,295.

Monday, 18 December 2017

Geriatric Women Sexuality Challenges Affecting Libido: A Case Study


Hispanic geriatric woman sexuality and libido are affected by hormonal imbalances; for example, low estrogen level causes physiological concerns such as, vaginal atrophy and vaginal dryness, among other symptoms. Also, comorbidities, such as diabetes, vascular diseases, hypertension, and hyperlipidemia are common diseases in the Hispanic menopausal woman. Another important aspect affecting libido is the psychological issue the Hispanic geriatric women population suffers, including depression, anxiety, or partner’s pressure for intercourse. In addition to physiological and psychological issues, medications’ side effects can also decrease the woman’s libido. Healthy lifestyles as well as controversial treatments have been shown to improve geriatric women sexual dysfunction and decreased libido.

Commonly, in all races the number of ageing woman is increasing. This is directly associated with life expectancy due to innovative treatments and the modern lifestyle. Ageing women usually out number older men; however, their sexuality and libido at menopause is still a taboo in the 21st century society. According to Bauer et al., it is clear that sexuality is an important component of quality of life for many older people and can be just as fulfilling as it is for younger people. Geriatric women sexual dysfunction is a symptom that a majority of geriatric women 65 years old or older complains about it in the outpatient setting. According to Abernethy et al., the prevalence of sexual dysfunction in postmenopausal women is even higher, with rates between 68% and 86.5%. Some women express their menopausal symptoms as vaginal dryness, low or not sexual desire, depression, anger, and/or anxiety due to partner pressure for intercourse.

This case study is based in a geriatric Hispanic woman suffering menopausal symptoms. It would cover physical factors such as, vaginal dryness and psychological factors corresponding to depression affecting women geriatric population. According to Watters et al., being able to remain sexually active often indicates greater self-worth, prevents social disengagement and avoids depression. Vaginal dryness and depression cause geriatric women sexual dysfunction. In addition to the mentioned causes, there are many other factors that can affect the changes in sexual desires in this population. For instance, socio-cultural factors, stress, traumas, and medications adverse effects are some reasons of women decrease libido. Attitudes toward sex are a cause of social and sexual experiences.

Friday, 15 December 2017

Frequency of Congenital Heart Defects in Indian Children with Down Syndrome


Congenital Heart Diseases (CHD) are commonly associated with Down Syndrome (DS) infants. Our study aimed at determining the occurrence and pattern of CHD in association with DS among patients in Indian subjects. A total of 60 patients with clinical features suggestive of DS were recruited. Echocardiography, standard karyotype and QF-PCR (Quantitative – Flourescent PCR) studies were performed in all patients in order to confirm DS. CHDs were detected in the 50% of children with DS. The commonest type of CHD reported in Indian subjects was atrioventricular septal defect (50%). The second most type of CHD present was ventricular septal defect (26.6%). Other type of CHD included in our study was atrial septal defect, tetralogy of fallot and patent ductus arteriosus with the frequency of 10 %, 6.6 % and 6.6% respectively. Our findings showed that CHDs are common in Indian DS children. These results suggest that a routine echocardiography should be mandatory in DS patients.

 Down Syndrome (DS) or trisomy 21 is a chromosomal disorder associated with a varied combination of morphological and structural birth defects. These defects include congenital mental disability, hypotonia, characteristic body features, congenital heart defects, Hirschsprung’s diseases and others. The frequency and severity of these morphological and functional defects vary significantly among affected individuals. DS affects about one in 700 live births.
Congenital heart defect disorder or CHD is a common defect among newborn infants [3] which can be caused by environmental or genetic factors. About 50% of babies with DS are born with CHD, which is a much higher percentage compared to the number of children without DS who are born with CHD which is approximately 1%. The most common CHD seen in infants with DS is an Atrioventricular Septal Defect (AVSD), or AV canal. Other heart defects seen in infants with DS include Ventricular Septal Defects (VSD), Atrial Septal Defects (ASD), Tetralogy of Ffallot (TOF) and Patent Ductus Arteriosus (PDA). However, the exact etiology of CHD in DS remains poorly understood. Few decades ago the frequency of CHD in DS was estimated to be approximately 20%, but now with the use of better diagnostic tool, the frequency estimated has increased to 50%. The most common CHD in the western literature is atrioventricular septal defects.

This hospital based descriptive study was conducted in department of Genetics, SGPGIMS, Lucknow Uttar Pradesh and department of Pediatrics, Post Graduate Institute of Medical Education and Research, PGIMER, Chandigarh. Total sixty DS children with age 0-15 years were included in this study. All patients were diagnosed based on 2- dimensional echocardiography for CHD and molecularly confirmed for DS using karyotyping in combination with QF-PCR. Exclusion criteria were race other than Indian. All the participants were of Indian the same ethnic origin and this study was approved by the Institutional Ethics Committee of Sanjay Gandhi Post Graduate Institute of Medical Sciences, SGPGI, Lucknow, and Uttar Pradesh. Presence of CHD and type of CHD were recorded as potential risk factors of DS. DS infants were as categorized under two groups: CHD and non CHD.

Thursday, 14 December 2017

Risk Factors of Surgical Recurrence after Resection for Crohn’s Disease

                                                      Austin Journal of Gastroenterology

Objective: The surgery is required in more than 80% of patients with Crohn’s disease. Crohn’s disease is associated with high rates of postoperative recurrence. The aim of the study was to identify, the risk factors of postoperative ‘surgical recurrence’ after the first resection for Crohn’s disease.
Methodology: We report a retrospective study from January 1998 to September 2010 that studied 226 patients originated only from Tunisia (in North Africa), operated on for MC. We had been interested to the risk factor of surgical recurrence of Crohn’s disease.
Results: Mean age was 33 years. The average time between the onset of the disease and the surgical procedure was 31 months. The diagnosis of CD was established preoperatively in 213 patients (94%). The diagnosis was made intraoperatively because of an acute complication in 5 cases (2.2%) and postoperatively in 8 cases (3.5%). The most common location was the ileocecal junction in 184 cases (81.4%). The most common type of lesion was the mixed form (stricture and fistula) in 123 cases (54.4%). Operative mortality was 0.04% (n=1). Specific morbidity was 8.4% (n=19). In long term, a surgical recurrence was noted in 18 patients (8%). In multivariate analysis, independent risk factors for recurrence were: smoking (p=0.012, ORs=3.57) and post-operative medical treatment (p=0.05, ORs=2.6).
Conclusion: Our series is unique for a lower rate of the postoperative recurrence (8%). The two risk factors of recurrence are smoking and the necessity of postoperative medical prophylaxis.
The surgery is required in more than 80% of patients with Crohn’s disease (CD) [1]. The aim of surgery is to treat complicated lesions [2]. The most important principle of the surgery is to perform an intestinal resection as limited as possible. Crohn’s disease is associated with high rates of postoperative recurrence. At 10 years after surgery, 75% of patients suffer recurrence and 45% of these require re-intervention. The aim of the study was to identify, the risk factors of postoperative ‘surgical recurrence’ after the first resection for Crohn’s disease.

This is a retrospective study, with prospective collection of data, conducted from January 1998 to September 2010, which included all patients undergoing surgery for primary CD. All patients born and living in Tunisia in North Africa. The diagnosis of CD was confirmed in all cases by histological examination of endoscopic biopsies or specimen after bowel resection. We excluded from this study, patients initially operated in another center and patients operated on for isolated anoperineal lesions of CD. The management was multidisciplinary and standardized for all patients.

Wednesday, 13 December 2017

Effect of Ammonium Sulphate Foliar Spray on Grain Yield and Yield Quality of Canola


The experiment entitle “Effect of Ammonium Sulphate Foliar Spray on Grain Yield And Yield Quality of Canola” was conducted at the Palatoo Research farm Department of Agronomy, Amir Muhammad Khan Campus, Mardan during rabi season 2014-15. The treatments consist of Ammonium Sulphate (AS) 1%, 0.2%, 0.3% solution and water spray as control. The experiment layed out in randomized complete block design with four replications. The results indicated that application of 1% AS improved grain yield 3177 (control) to 3423 (treated), oil content 42.3% (control) to 45.7% (treated), gluccosinulates 65.2 micro mol gm-1 (control) to 70.1 micro mol gm-1 (treated), protein content 23.1% (control) to 23.6% (treated), grain Sulphur % 0.29 (control) to 0.32 (treated) and grain nitrogen %3.35 (control) to 3.89% of (treated). The application of AS 0.2% produced grain yield (3342 kg ha-1) oil content (43.2%) gluccosinulates (62.8micro mol gm-1) protein content (23.4%) grain Sulphur (0.30%) and grain nitrogen (3.11%). While the application of AS 0.3% produced grain yield (3245 kg ha-1) oil content (44.2%) gluccosinulates (67.1 micro mol gm-1) protein content (2.5%) grain Sulphur (0.31%) and grain nitrogen (3.0%). Therefore on the basis of this research at 1% AS is suggested for application on canola to improve its grain yield and yielding quality components.

 Rapeseed (Brassica napus L.) belongs to the Cruciferae family the common species are Nigra, Carinata, juncea, oleracea and compestries. Rapeseed or mustard was grown from 300 Bc in Indus valley of Pakistan as a fodder crop. Rapeseed and mustard are traditional oil seed crops of Pakistan are grown in large area of four provinces of country. Canola was introduced in Pakistan during 1995 for general cultivation to replace traditional oilseed crops like rapes and mustards because of its low erucic acid contents and high yielding capacity. During 2011-12 in Pakistan the Canola crop was cultivated 14700 ha with the production of 7000 tones, while Khyber Pakhtunkhwa the area under cultivation was 1300 ha with a total production of 1800 tones.

Like all other crops, growth, developmental process and grain yield of canola depends upon biotic and a biotic factors. Sulfur is the fourth major plant nutrient after nitrogen, phosphorus and potassium. It is essential for synthesis of the amino acids like cystine and methionine, a component of vitamin A and activates certain enzyme systems in plants. Edible oil is one of the basic requirements of our daily diet. Pakistan is suffering from acute deficiency in edible oil because of its increased consumption. The total availability of edible oil was 2.821 million tons. Local production of edible oil stood at 0.68 million tons, which is 24 percent of the total availability in the country. Sulphur has been reported to influence productivity of oil seed.

Tuesday, 12 December 2017

Fatal Pulmonary Tumour Thrombotic Microangiopathy (PTTM) Associated with Signet Ring Cell Carcinoma of Colon: An Autopsy Diagnosis

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare clinicopathological entity in which the tumor cells embolize to the pulmonary vasculature leading to fibro cellular intimal thickening and arteriolar occlusion by cellular intimal proliferation. Sub-acute respiratory failure, pulmonary hypertension, right sided heart failure and sudden death may be seen due to consequences of stenosis of blood vessels.
We describe a case of a 23 year old man who presented with alleged history of found unconscious and declared brought death. He was clinically diagnosed as refectory sepsis with ventilator associated pneumonia with acute kidney injury. Past history revealed Crohn’s disease and treatment with Azathioprine and prednisolone. Mucicarmine was positive in colonic tumor as well as in pulmonary tumor cell emboli with recanalization and intimal fibro cellular proliferation of small arteries. A postmortem diagnosis of poorly differentiated signet ring cell carcinoma of colon with PTTM was made based on autopsy results.
Unfortunately, PTTM is difficult to diagnose and is mostly a post mortem diagnosis with an extremely poor prognosis. Pulmonary hypertension due to metastatic tumor emboli should be included in the differential diagnosis of various causes of dyspnea in patients with cancer.
Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare clinicopathological entity in which the tumor cells embolize, organize and recanalize to the pulmonary vasculature leading to fibro cellular intimal thickening and vessel stenosis. Sub-acute respiratory failure, pulmonary hypertension, right sided heart failure and sudden death may be seen due to consequences of stenosis of blood vessels caused by PTTM. In this report, we describe a rare case of PTTM associated with metastatic colon carcinoma diagnosed on postmortem examination of a young man. We also aim to review the literature related to PTTM and associated malignancies and how they were diagnosed and managed.

Monday, 11 December 2017

The Comparison of Muscle Timing between Athletes with and without Chronic Ankle Instability during Lateral Jump Landing


Most studies have investigated peroneal reaction time in relevant conditions of unexpected inversion perturbation occurring. The need to conduct more functional and dynamic testing that closely mimics athletic performances has been emerged.The aim of present study was to compare premotor time and motor time of leg muscles between athletes with and without chronic ankle instability during landing phase of a lateral jump condition.Twelve athletes with self-reported unilateral chronic ankle instability and 12 matched controls participated in the study. Participants performed lateral jump landing test during a relatively simple dynamic choice reaction task.An electromyography device synchronized with a force plate collected data during the landing phase of lateral jump. Premotor time, motor time and reaction time of leg muscles were recorded and group differences were assessed.
Mean premotor time values for peroneus longus and tibialis anterior muscles were significantly (P=0.000, P= 0.035 respectively) greater in chronic ankle instability patients compared to controls. There was astatistically significant (p=0 .001, P= 0.014 respectively) decrease in motor time measures for peroneus longus and brevis muscles in chronic ankle instability group compared to control group. There was no statistically significant difference in reaction time between the 2 groups.This study found muscle timing deficits in injured ankles of athletes with chronic ankle instability compared to healthy ones. The greater premotor time delay of peroneus longus and tibialis anterior muscles demonstrated in subjects with ankle instability in compared to healthy athletes should be taken in to consideration during assessment and rehabilitation programs.
Ankle sprains are one of the most common injuries affecting athletes. Many ankle injuries are found in sports that require jumping and landing such as basketball, volleyball and soccer. Ankle sprains account for up to 25% of all lost time from participation in sport competitions. People who experience an ankle sprain are at risk of developing Chronic Ankle Instability (CAI) which is characterized by subjective, repeated episodes of giving way after an initial ankle sprain. It has been estimated that up to 80% of athletes experience a recurrent sprain. Symptoms of residual instability represent in 20-40% of patients and this can lead to osteoarthritis in long term. Proprioception, muscle strength, muscle reaction time, and postural control are the factors contributing to impaired neuromuscular control that is believed to be the main cause of ankle instability development.

Friday, 8 December 2017

Emergency Dialysis in End-Stage Renal Disease: Incidence and Characteristics in La Paz, Baja California Sur

According to international guidelines of Kidney Disease: Improving Global Outcomes (KDIGO, 2012); chronic renal failure (CRF) is defined as those abnormalities of kidney structure or function, present for more than 3 months with implications for health. CRF is classified according to cause, category of glomerular filtration rate (GFR) and category of albuminuria. The estimated prevalence of CRF is 16.8% worldwide. CRF can progress to end-stage renal disease (ESRD), which requires dialysis or transplantation. However, many patients cannot undergo such therapies because of its high cost [2- 3].Complications of CRF include dialytic emergency, anemia, renal osteodystrophy and malnutrition, among others.
CRF is a highly prevalent pathology that affects people of all races, nationalities, age, gender and economic level. Low socioeconomic status and poor access to health services contribute to inequality in health care and exacerbate negative effects of genetic or biological predisposition [5-6]. It is precisely the people with little or no access to health services who are at greater risk for complications of CRF.
According to annual report of the United States Renal Data System, main causes of end-stage renal failure in patients with CRF are diabetes (153 cases per million inhabitants in 2009), arterial hypertension (99 cases per million inhabitants) and glomerulonephritis (23 cases per million inhabitants). Cardiovascular disease is also an important cause; however, about 28% of patients with clinically significant CRF (stage 3 or higher) are not diabetic or hypertensive, especially those older than 65 years. In developing countries, diabetes and hypertension are currently the leading causes of CRF with a prevalence of 30% and 21% respectively, but glomerulonephritis and CRF of unknown origin are responsible for a greater proportion of ESRD, especially in young patients.
In Mexico, CRF is one of main causes of morbidity and mortality and one of main causes of hospitalization in emergency departments. CRF is considered a catastrophic disease due to increasing number of cases, high investment costs, limited infrastructure and human resources, late detection and high morbidity and mortality rates in substitution programs. In Mexico, prevalence and incidence of patients with CRF is unknown and the precise number of patients in any of its stages, age groups and gender most affected is unknown. An incidence of 377 cases per million inhabitants and a prevalence of 1,142 per million is estimated. In Mexico there are about 52,000 patients on dialysis, of which 80% are treated at the Mexican Social Security Institute (IMSS).

Thursday, 7 December 2017

Risk of Lactic Acidosis in Diabetic Patients Taking Metformin and Who Receive Intravascular Iodinated Contrast Media

Due to thelarge number of patients who develop diabetes mellitus type 2 and the tendency to use radiological methods to avoid invasive procedures, it is becoming increasingly frequent to find patients undergoing metformin treatments who are being given intravascular iodinated contrast media. Traditionally, the fear that this can be linked to lactic acidosis has always existed, despite no proven evidence to support this theory.

The prevalence and incidence rate of diabetes mellitus type 2 is currently increasing; in most patients, the disease’s treatment is still based on the administering of metformin, along with a change of life style. Also, the number of patients who undergo radiological examinations, in which some form of intravascular iodinated contrast media is used, is increasing every day. Traditionally, metformin was withdrawn from those patients who needed to undergo studies involving intravascular iodinated contrast media due to the risk of developing lactic acidosis which, although not very frequent, has a very high mortality rate (40%). However, the evidence supporting this is based on isolated cases which have been researched using heterogeneous studies.

Intravascular iodinated contrast media are not a stand-alone risk factor of lactic acidosis in patients that take metformin, but rather they become relevant when other underlying kidney disorders are also present. Taking this into account, we can establish a causal link because the use of intravascular iodinated contrast media does suppose a risk of developing kidney failure; this risk can be stratified depending on each patient’s characteristics. According to this there is a possibility of developing contrast-induced nephropathy. A set of variables were established and given a value; according to the total sum, the risk of developing a nephropathy can be calculated. The variables were: systolic blood pressure below 80mmHg, intra-aortic balloon pump, grade 3-4 heart failure or a history of acute lung edema, being over 75 years of age, packed cell volume below 39% in men or below 36% in women, diabetes mellitus, contrast volume and glomerular filtration (which greatly affects the final assessment).

Wednesday, 6 December 2017

Guide for Morpholino Users: Toward Therapeutics

Morpholino oligos are uncharged molecules for blocking sites on RNA. They are specific, soluble, non-toxic, stable, and effective antisense reagents suitable for development as therapeutics and currently in clinical trials. They are very versatile, targeting a wide range of RNA targets for outcomes such as blocking translation, modifying splicing of pre-mRNA, inhibiting miRNA maturation and activity, as well as less common biological targets and diagnostic applications. Solutions have been developed for delivery into a range of cultured cells, embryos and adult animals; with development of a non-toxic and effective system for systemic delivery, Morpholinos have potential for broad therapeutic development targeting pathogens and genetic disorders.
Morpholino oligos bind to complementary sequences of RNA and get in the way of processes. Morpholino oligos are commonly used to prevent a particular protein from being made in an organism or cell culture. Morpholinos are not the only tool used for this: a protein’s synthesis can be inhibited by altering DNA to make a null mutant (called a gene knockout) or by interrupting processes on RNA (called a gene knockdown). Some DNA alterations cause production of a protein to decrease without stopping all production; confusingly, these are also called gene knockdowns. DNA alterations are permanent, while knockdowns of RNA are either transient, generally last several days after dosing with antisense (such as Morpholinos), or are long-term, depending on continued production of knockdown RNA in cells (such as shRNA transcribed in cells from a plasmid).
Morpholinos have been broadly used in the developmental biology community to knock down genes in embryos of organisms such as zebrafish (Danio rerio), African clawed frogs (Xenopus sp.), chicks (Gallus gallus), sea urchins (e.g. Strongylocentrotus sp.), sea squirts (Ciona sp.), and many more. The oligos are usually microinjected though fine glass needles into early embryos at the one-to-few cell stage. Many kinds of antisense have toxic effects during development of an embryo. Because Morpholinos have little interaction with protein they are unusually non-toxic antisense, sufficiently non-toxic to make them the first choice of most developmental biologists for transient gene knockdowns. In contrast, injection of oligos containing phosophorothioate intersubunit linkages often kills embryos. Morpholinos are highly specific antisense, having less interaction with unintended RNAs than antisense which employs protein activity; this is because a Morpholino must be complementary to a longer sequence of RNA than antisense using catalytic activity (e.g. RNAi, phosphorothioate RNA, etc.). Less specific antisense causes changes in gene expression during development of the embryo and can cause developmental defects (teratogenesis).

Tuesday, 5 December 2017

Gastric Plication for Repeated Gastric Band Prolapse after Endoscopic Treatment: A Case Report


Laparoscopic Adjustable Gastric Banding (LAGB) is a simple, safe and effective procedure for treating morbid obesity. However, several complications after LAGB have been reported, such as band erosion, prolapse, gastric perforation, abscess, tube disconnection, port flip down and infection.These complications could be the main cause of failure after LAGB. For this reason, revisional weight-loss surgery after failed LAGB might be considered. Band prolapse is a significant and common late complication after LAGB. We have performed endoscopic treatment of band prolapse as we reported.
However, band prolapse occurred repeatedly in two cases. We present a patient with repeated prolapses after endoscopic treatment that required gastric plication treatment. A 35-year-old woman with BMI (Body Mass Index) 40 underwent LAGB procedure to treat her obesity using the pars flaccida technique with no implication suture, and port placement under the anterior sheath of the rectus abdominis muscle. The patient presented a history of onset of band prolapse 22 months after the LAGB procedure. The symptoms of prolapse were sudden abdominal pain and repeated vomiting. An endoscopic procedure was performed after deflation of the band under intravenous anesthesia. Band prolapse was diagnosed and treated by endoscopy.
After a prolapsed stomach pouch was found, we inflated it with air. The prolapsed stomach pouch was gradually reduced as the stomach was inflated with air. The stomach was fully reduced and finally the band returned to its normal position. After reduction, the entire lumen of the stomach was examined to check its normality. However, the patient had the second episode of band prolapse that required endoscopic treatment five months after the first one. We treated it with the same endoscopic technique as above. The patient had recurrence that was treated by the endoscopic reduction technique 13 months after the second episode. The third endoscopic treatment of band prolapse was performed for an hour resulting in failure. She was sent to operating room and underwent laparoscopic reduction with two-row gastric plication. The gastric greater curvature was plicated using 2/0 prolen from fundus at the level of diaphragm preserving the His angle to 10cm proximal to the pylorus. It took 70min for the whole procedure with 3 trocars under general anesthesia. The patient was discharged in good condition 3 days after surgery. Fifteen months later, there was no evidence of recurrence.

Not all anterior band prolapses have reduced by band deflation and endoscopic approach. When we found any sign of infection or perforation inside the stomach, we fixed it operatively. Otherwise, almost all the band prolapses after such sutureless LAGB without delay in diagnosis can be fixed easily with an endoscopic procedure. Those patients with repeated band prolapses could be treated by onerow or two-row plication technique. The gastric greater curvature was plicated using 2/0 prolen from fundus at the level of diaphragm preserving the His angle to 10cm proximal to the pylorus. The aim of the plication was restriction of the prolapsed portion of the stomach via folds from its own wall. However, we need long term followup to evaluate the efficacy of the gastric plication and endoscopic treatment of the band prolapse.

Monday, 4 December 2017

Nanotechnology- A Promising Approach for Suicide Gene Therapy

Cancer is one of the world’s most dreadful diseases and the battle against cancer continues till date. Suicide gene therapy for cancer is one of the best approaches for annihilation of cancer. In brief, suicide gene codes for an enzyme which converts a nontoxic prodrug into toxic metabolites and subsequently mediates death of host cells itself on account of which it is named “suicide” gene therapy. These suicide gene when constitutively expressed by the cells not only mediates death of host cells but also inflicts strong bystander effects on neighboring cells by predisposing them to toxic downstream metabolites. Due to such advantages, they manifest minimal systemic toxicity and are also effective against many drug resistance cancer cells. Among all existing suicide genes, Cytosine Deaminase (CD) and Herpes Simplex Virus-thymidine kinase (HSVtk) have shown promising results initially and has been investigated extensively since long. The HSVtk enzyme initially phosphorylates the prodrug Ganciclovir (GCV) to its monophosphate form, which is subsequently phosphorylated again by endogenous cellular kinase to generate nucleotide analogs (di- and triphosphate forms of GVC). Triphosphate form of GCV is then readily incorporated into DNA during the course of DNA synthesis and acts as a chain terminator to prevent further DNA synthesis, which ultimately induces cell death.

The therapeutic efficacy of HSVtk suicide gene therapy is often limited by cell-to-cell contact which is a prerequisite for transport of downstream metabolic byproducts of ganciclovir to neighboring cells so as to attain bystander-killing effect. As an outcome of such drawbacks, HSVtk suicide gene does not seem to be effective against different cell types. In contrary to this, Cytosine Deaminase (CD) efficiently converts prodrug 5-Fluorocytosine (5- FC) into therapeutically active anticancer agent 5-Fluorouracil (5- FU), which subsequently permeates across the cell membrane to mediate bystander killing effects on adjacent neighboring cells. Thus, 5-FC/CD system attains suicide gene therapy much more efficiently as compared to other counterparts. Although 5-FC/CD system attains better therapeutic outcomes, it is ineffective against 5-FC resistant cancer cells and thus its anticancer potential could not be generalized for all cancer types. In order to overcome such drawback, Gopinath et al. have designed Cytosine Deaminase-Uracil Phosphoribosyltransferase (CD-UPRT) bifunctional suicide gene construct in which Uracil Phosphoribosyltransferase (UPRT) acts upon product of CD i.e. 5-FU and converts it further into other toxic metabolites.

The therapeutic effect of suicide genes can be enhanced by combinatorial approaches. In combination therapy, two or more drugs with similar or different mode of action are employed to realize synergistic anticancer therapeutic potentials. Such synergistic anticancer potential of combination of radiation therapy and 5-FC/ CD plus UPRT gene therapy was demonstrated by Kambara et al. against malignant gliomas [8]. Apart from this, the combination therapy also provides scope for exploiting radio sensitizing properties of 5-FU and by stander effects during the course of treatment. Many research groups have reported the use of suicide gene in combination with chemotherapy and radiation to enhance the therapeutic effect and to overcome the drug resistance. Gopinath et al. were the first to report the applications of silver nanoparticles for synergizing the therapeutic effect of suicide gene. They have also reported the synergistic therapeutic effect of suicide gene with anticancer drug curcumin. One of the major challenging tasks in suicide gene therapy is lack of suitable vectors for targeted delivery of suicide gene to cancer cells. The application of such DNAbased therapeutics is largely limited due to poor cellular uptake, degradation by serum nucleases and rapid renal clearance following systemic administration. In addition to these, organ specific targeted DNA therapy has been a major challenge to overcome off-target gene therapy. In order to circumvent these limitations, numerous organ specific targeted nanocarriers have been developed recently for systemic administration.

Tuesday, 28 November 2017

Structure Activity Study of Clinically Observed Adverse Events and Oligomer Chemistry

The number and diversity of new nucleic acid based therapeutics in clinical trial illustrates the remarkable flexibility of this approach to therapy. The use of synthetic oligomers has the advantage of control of dose and duration of action over gene therapy and Cas9/CRISPR approaches that are developed in parallel. Further, synthetic compounds may contain a variety of modifications to fine tune their therapeutic purpose and define their mechanism of action. The expansion in diversity of nucleic acid therapeutics may also reflect the approaches to barriers observed in previous clinical trials. The objective of this review is to provide new insight into the clinical adverse event data reported for nucleic acid based therapeutics in advanced development, with the goal of establishing a comprehensive framework for evaluating the current implications, and future direction, of therapeutic antisense technologies. A pattern of adverse events, some sufficiently severe to require discontinuation of treatment, include Flu-Like Symptoms (FLS), Injection Site Reactions (ISR), kidney abnormalities, elevated liver enzymes, and thrombocytopenia are frequently observed with oligomer chemistries that have negatively charged phosphate linkages and naturally occurring sugars. Anti-Drug Antibodies (ADA) have been reported in high percentages following chronic treatment with oligomer chemistries designed to enhance duration of tissue residence time. However, these common adverse events are not observed with Phosphorodiamidate Morpholino Oliogmers (PMO) containing morpholino sugars and no negative charge in the phosphate linkage.
Oligonucleotide drug development must be viewed through a lens, which recognizes that humans are well equipped to recognize both foreign and endogenous DNA/RNA in the circulation. This protective recognition arises either as part of an innate, microbial DNA immune response or in response to cellular danger signaled by DNA Damage-Associated Molecular Patterns (DAMPs) [1,2]. Now that synthetic analogues of DNA and RNA are being developed as therapeutics for both acute and chronic treatment regimens, it is critical that we clarify the extent to which these emerging therapeutics result in chronic or inappropriate activation of these nucleic-acid sensors.

Information available to guide optimal therapeutic oligomer chemistry has transitioned from what chemical structures can be made to properties in biological systems and then on to efficacy in animal models. Recently, advanced therapeutic development of oligonucleotides has provided a wealth of information from well controlled clinical trials. Human data are the most pertinent information as, in some cases, the preclinical efficacy reports are discordant with human efficacy observations such as the case with TKM-100802 which was highly effective in nonhuman primates  but its use in patients from the recent Ebola outbreak were not effective  and off-target effects including activation of inflammatory cytokines were notable outcomes. In addition, detailed summaries are only recently publicly available for Ampligen, mipomersen, drisapersen, and eteplirsen which provide comprehensive evaluation of efficacy and safety from multiple human studies.

Monday, 27 November 2017

An Association of Insulin Resistance with Numerous of Circulating Microparticles Originated from Endothelial Cells in Cardiac Failure Individuals without History of Diabetes Mellitus

ACEI: Angiotensin-Converting Enzyme Inhibitors; ARBs: Angiotensin Receptor Blockers; AUC: Area Under Curve; BMI: Body Mass Index; BNP: Brain Natriuretic Peptide; CHF: Chronic Heart Failure; CV: Cardiovascular; EMPs: Endothelial-Derived Microparticles; GFR: Glomerular Filtration Rate; hs-CRP: High Sensitive C-Reactive Protein; HbA1c: Glycated Hemoglobin; HDL-C: High-Density Lipoprotein Cholesterol; HFpEF: CHF with Precerved LVEF; HFrEF: CHF with Reduced LVEF; IR: Insulin Resistance; LDL-C: Low-Density Lipoprotein Cholesterol; LVEF: Left Ventricular Ejection Fraction; MetS: Metabolic Syndrome; T2DM: Type 2 Diabetes Mellitus.

 Chronic heart failure (CHF) remains a major public health problem worldwide leading to growth of cardiovascular (CV) morbidity and mortality. During the past decades prevalence and incidence of CHF has increased. Despite contemporary understanding of the underlying disease mechanisms of CHF there is knowledge gap with respect to nature evolution CHF under influence of co-existing CV risk factors. Indeed, the results of few population-based and epidemiological investigations have shown that multiple actual CV risk factors and various metabolic comorbidities presented in CHF patients may affect cardiac failure development. There is still debate in the scientific community about whether identification of numerous of CV risk factors / the metabolic co-morbidities improves ability to predict CHF development beyond use of single risk factor.
Recent clinical investigations have revealed insulin resistance (IR) is as a distinct cause of cardiac dysfunction and CHF in diabetic and non-diabetic patients. IR mediates excessive or inadequate proliferation of the extracellular matrix accelerates apoptosis via increased oxidative stress, neurohumoral and inflammatory activation that effect cardiac remodeling and endothelial function. Despite IR is considered a main component of metabolic syndrome (MetS) and type two diabetes mellitus (T2DM), a lot of individuals with CHF may present IR prior to other dysmetabolic conditions including MetS / T2DM. However, IR is persisted component of CV risk factors and it role in CHF development in the patients without history of T2DM is still unclear.