The superior efficacy of chloroquine over buparvaquone in reducing the chronic cerebral Toxoplasma gondii cysts load and improving the ultrastructural pathology in an immunocompromised murine model

@#Toxoplasma gondii, the etiologic agent of toxoplasmosis, infects about 30 – 50% of the world population. The currently available anti-Toxoplasma agents have serious limitations. The present study aimed to investigate the effects of two antimalarials; buparvaquone (BPQ) and chloroquine (CQ), on immunocompromised mice with chronic cerebral toxoplasmosis, using spiramycin as a reference drug. The assessed parameters included the estimation of mortality rates (MR) among mice of the different study groups, in addition to the examination of the ultrastructural changes in the brain tissues by transmission electron microscopy. The results showed that only CQ treatment could decrease the MR significantly with zero deaths, while both spiramycin and BPQ caused an insignificant reduction of MR compared to the infected non-treated group. All the used drugs decreased the number of mature ruptured cysts significantly compared to the infected non-treated group, while only CQ increased the number of atrophic and necrotic cysts significantly. Furthermore, both spiramycin and BPQ improved the microvasculopathy and neurodegeneration accompanying the infection with different degrees of reactive astrocytosis and neuronal damage with the best results regarding the repair of the microvascular damage with less active glial cells, and normal neurons in the CQ-treated group. In conclusion, this study sheds light on CQ and its excellent impact on treating chronic cerebral toxoplasmosis in an immunocompromised mouse model.

Thalassemia, a human blood disorder / Talassemia, uma doença do sangue humano

A group of inherited blood defects is known as Thalassemia is among the world's most prevalent hemoglobinopathies. Thalassemias are of two types such as Alpha and Beta Thalassemia. The cause of these defects is gene mutations leading to low levels and/or malfunctioning α and β globin proteins, respectively. In some cases, one of these proteins may be completely absent. α and β globin chains form a globin fold or pocket for heme (Fe++) attachment to carry oxygen. Genes for alpha and beta-globin proteins are present in the form of a cluster on chromosome 16 and 11, respectively. Different globin genes are used at different stages in the life course. During embryonic and fetal developmental stages, γ globin proteins partner with α globin and are later replaced by β globin protein. Globin chain imbalances result in hemolysis and impede erythropoiesis. Individuals showing mild symptoms include carriers of alpha thalassemia or the people bearing alpha or beta-thalassemia trait. Alpha thalassemia causes conditions like hemolytic anemia or fatal hydrops fetalis depending upon the severity of the disease. Beta thalassemia major results in hemolytic anemia, growth retardation, and skeletal aberrations in early childhood. Children affected by this disorder need regular blood transfusions throughout their lives. Patients that depend on blood transfusion usually develop iron overload that causes other complications in the body systems like renal or hepatic impairment therefore, thalassemias are now categorized as a syndrome. The only cure for Thalassemias would be a bone marrow transplant, or gene therapy with currently no significant success rate. A thorough understanding of the molecular basis of this syndrome may provide novel insights and ideas for its treatment, as scientists have still been unable to find a permanent cure for this deadly disease after more than 87 years since it is first described in 1925.

Um grupo de defeitos sanguíneos hereditários é conhecido como talassemia e está entre as hemoglobinopatias mais prevalentes do mundo. As talassemias são de dois tipos, como talassemia alfa e beta. As causas desses defeitos são as mutações genéticas que levam a níveis baixos e/ou proteínas de globina com mau funcionamento, respectivamente. Em alguns casos, uma dessas proteínas pode estar completamente ausente. As cadeias de globina α e β formam uma dobra ou bolsa de globina para a fixação de heme (Fe ++) para transportar oxigênio. Os genes das proteínas alfa e beta globina estão presentes na forma de um cluster nos cromossomos 16 e 11, respectivamente. Diferentes genes de globina são usados em diferentes estágios do curso de vida. Durante os estágios de desenvolvimento embrionário e fetal, as proteínas γ globina se associam à α globina e, posteriormente, são substituídas pela proteína β globina. Os desequilíbrios da cadeia de globina resultam em hemólise e impedem a eritropoiese. Indivíduos que apresentam sintomas leves incluem portadores de talassemia alfa ou as pessoas com traços de talassemia alfa ou beta. A talassemia alfa causa condições como anemia hemolítica ou hidropsia fetal fatal, dependendo da gravidade da doença. A beta talassemia principal resulta em anemia hemolítica, retardo de crescimento e aberrações esqueléticas na primeira infância. As crianças afetadas por esse distúrbio precisam de transfusões de sangue regulares ao longo da vida. Os pacientes que dependem de transfusão de sangue geralmente desenvolvem sobrecarga de ferro que causa outras complicações nos sistemas do corpo, como insuficiência renal ou hepática, portanto as talassemias agora são classificadas como uma síndrome. A única cura para as talassemias seria um transplante de medula óssea ou terapia genética sem atualmente uma taxa de sucesso significativa. Uma compreensão completa da base molecular dessa síndrome pode fornecer novos insights e ideias para seu tratamento, [...].

Thalassemia, a human blood disorder

Abstract A group of inherited blood defects is known as Thalassemia is among the worlds most prevalent hemoglobinopathies. Thalassemias are of two types such as Alpha and Beta Thalassemia. The cause of these defects is gene mutations leading to low levels and/or malfunctioning and globin proteins, respectively. In some cases, one of these proteins may be completely absent. and globin chains form a globin fold or pocket for heme (Fe++) attachment to carry oxygen. Genes for alpha and beta-globin proteins are present in the form of a cluster on chromosome 16 and 11, respectively. Different globin genes are used at different stages in the life course. During embryonic and fetal developmental stages, globin proteins partner with globin and are later replaced by globin protein. Globin chain imbalances result in hemolysis and impede erythropoiesis. Individuals showing mild symptoms include carriers of alpha thalassemia or the people bearing alpha or beta-thalassemia trait. Alpha thalassemia causes conditions like hemolytic anemia or fatal hydrops fetalis depending upon the severity of the disease. Beta thalassemia major results in hemolytic anemia, growth retardation, and skeletal aberrations in early childhood. Children affected by this disorder need regular blood transfusions throughout their lives. Patients that depend on blood transfusion usually develop iron overload that causes other complications in the body systems like renal or hepatic impairment therefore, thalassemias are now categorized as a syndrome. The only cure for Thalassemias would be a bone marrow transplant, or gene therapy with currently no significant success rate. A thorough understanding of the molecular basis of this syndrome may provide novel insights and ideas for its treatment, as scientists have still been unable to find a permanent cure for this deadly disease after more than 87 years since it is first described in 1925.

Resumo Um grupo de defeitos sanguíneos hereditários é conhecido como talassemia e está entre as hemoglobinopatias mais prevalentes do mundo. As talassemias são de dois tipos, como talassemia alfa e beta. As causas desses defeitos são as mutações genéticas que levam a níveis baixos e/ou proteínas de globina com mau funcionamento, respectivamente. Em alguns casos, uma dessas proteínas pode estar completamente ausente. As cadeias de globina e formam uma dobra ou bolsa de globina para a fixação de heme (Fe ++) para transportar oxigênio. Os genes das proteínas alfa e beta globina estão presentes na forma de um cluster nos cromossomos 16 e 11, respectivamente. Diferentes genes de globina são usados em diferentes estágios do curso de vida. Durante os estágios de desenvolvimento embrionário e fetal, as proteínas globina se associam à globina e, posteriormente, são substituídas pela proteína globina. Os desequilíbrios da cadeia de globina resultam em hemólise e impedem a eritropoiese. Indivíduos que apresentam sintomas leves incluem portadores de talassemia alfa ou as pessoas com traços de talassemia alfa ou beta. A talassemia alfa causa condições como anemia hemolítica ou hidropsia fetal fatal, dependendo da gravidade da doença. A beta talassemia principal resulta em anemia hemolítica, retardo de crescimento e aberrações esqueléticas na primeira infância. As crianças afetadas por esse distúrbio precisam de transfusões de sangue regulares ao longo da vida. Os pacientes que dependem de transfusão de sangue geralmente desenvolvem sobrecarga de ferro que causa outras complicações nos sistemas do corpo, como insuficiência renal ou hepática, portanto as talassemias agora são classificadas como uma síndrome. A única cura para as talassemias seria um transplante de medula óssea ou terapia genética sem atualmente uma taxa de sucesso significativa. Uma compreensão completa da base molecular dessa síndrome pode fornecer novos insights e ideias para seu tratamento, já que os cientistas ainda não conseguiram encontrar uma cura permanente para essa doença mortal depois de mais de 87 anos desde que foi descrita pela primeira vez em 1925.

Thalassemia, a human blood disorder / Talassemia, uma doença do sangue humano

Abstract A group of inherited blood defects is known as Thalassemia is among the world's most prevalent hemoglobinopathies. Thalassemias are of two types such as Alpha and Beta Thalassemia. The cause of these defects is gene mutations leading to low levels and/or malfunctioning α and β globin proteins, respectively. In some cases, one of these proteins may be completely absent. α and β globin chains form a globin fold or pocket for heme (Fe++) attachment to carry oxygen. Genes for alpha and beta-globin proteins are present in the form of a cluster on chromosome 16 and 11, respectively. Different globin genes are used at different stages in the life course. During embryonic and fetal developmental stages, γ globin proteins partner with α globin and are later replaced by β globin protein. Globin chain imbalances result in hemolysis and impede erythropoiesis. Individuals showing mild symptoms include carriers of alpha thalassemia or the people bearing alpha or beta-thalassemia trait. Alpha thalassemia causes conditions like hemolytic anemia or fatal hydrops fetalis depending upon the severity of the disease. Beta thalassemia major results in hemolytic anemia, growth retardation, and skeletal aberrations in early childhood. Children affected by this disorder need regular blood transfusions throughout their lives. Patients that depend on blood transfusion usually develop iron overload that causes other complications in the body systems like renal or hepatic impairment therefore, thalassemias are now categorized as a syndrome. The only cure for Thalassemias would be a bone marrow transplant, or gene therapy with currently no significant success rate. A thorough understanding of the molecular basis of this syndrome may provide novel insights and ideas for its treatment, as scientists have still been unable to find a permanent cure for this deadly disease after more than 87 years since it is first described in 1925.

Resumo Um grupo de defeitos sanguíneos hereditários é conhecido como talassemia e está entre as hemoglobinopatias mais prevalentes do mundo. As talassemias são de dois tipos, como talassemia alfa e beta. As causas desses defeitos são as mutações genéticas que levam a níveis baixos e/ou proteínas de globina com mau funcionamento, respectivamente. Em alguns casos, uma dessas proteínas pode estar completamente ausente. As cadeias de globina α e β formam uma dobra ou bolsa de globina para a fixação de heme (Fe ++) para transportar oxigênio. Os genes das proteínas alfa e beta globina estão presentes na forma de um cluster nos cromossomos 16 e 11, respectivamente. Diferentes genes de globina são usados ​​em diferentes estágios do curso de vida. Durante os estágios de desenvolvimento embrionário e fetal, as proteínas γ globina se associam à α globina e, posteriormente, são substituídas pela proteína β globina. Os desequilíbrios da cadeia de globina resultam em hemólise e impedem a eritropoiese. Indivíduos que apresentam sintomas leves incluem portadores de talassemia alfa ou as pessoas com traços de talassemia alfa ou beta. A talassemia alfa causa condições como anemia hemolítica ou hidropsia fetal fatal, dependendo da gravidade da doença. A beta talassemia principal resulta em anemia hemolítica, retardo de crescimento e aberrações esqueléticas na primeira infância. As crianças afetadas por esse distúrbio precisam de transfusões de sangue regulares ao longo da vida. Os pacientes que dependem de transfusão de sangue geralmente desenvolvem sobrecarga de ferro que causa outras complicações nos sistemas do corpo, como insuficiência renal ou hepática, portanto as talassemias agora são classificadas como uma síndrome. A única cura para as talassemias seria um transplante de medula óssea ou terapia genética sem atualmente uma taxa de sucesso significativa. Uma compreensão completa da base molecular dessa síndrome pode fornecer novos insights e ideias para seu tratamento, já que os cientistas ainda não conseguiram encontrar uma cura permanente para essa doença mortal depois de mais de 87 anos desde que foi descrita pela primeira vez em 1925.

Evaluation, preparation, and description of chitosan nanoparticles, as well as improving rivaroxaban bioavailability

The aim of the present study is the Evaluation, preparation, and description of chitosan nanoparticles and bioavilibility enhancement of rivaroxaban. Preparation of Rivaroxaban nanoparticles (RB-NPs) were prepared by the ionic gelation method. Different parameters were studied for evaluation, Preparation & description of nanoparticles. The results of the present study showed that the formulation F7 showed the significant results for all the selected parameter as compared to the other formulations. The formulation F1, F5, and F6 showed the highest production yield (52.5, 52.35, and 52.35% respectively) and F7 showed the significant production yield (51.85%), zeta-potential (23.63 mV), entrapment efficiency (99.87), particle size (316.12±2.14 nm) and poly disparity index (0.32). Nanoparticles are solid colloidal drug carriers ranging from 10—1000 nm in diameter and are composed of synthetic, natural or semi-synthetic polymers encapsulating the drug molecule.

Hematological Profile with Peripheral Blood Smear Morphology of Admitted COVID-19 Infected Patients: A Study at a COVID Dedicated Hospital in Kashmir

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection started in Wuhan, China, and spread to the rest of the world to become a pandemic affecting over 385 million people throughout the world to date. Coronavirus disease 2019 (COVID-19) is primarily started as a respiratory tract infection. Recent studies indicate that it should be regarded as a systemic disease involving multiple systems including the hematopoietic system. Complete blood count and its parameters are important investigative tools in its prognosis. However, very few studies highlight the importance of peripheral blood cell morphology in this disease. Aim: To study the hematological parameters (complete blood count and peripheral blood film) of COVID-19-positive patients and to compare the hematological parameters of those admitted in intensive care units (ICUs) with those admitted in non-ICUs of the hospitals. Materials and methods: This retrospective study was carried out at a COVID-19 dedicated tertiary care center over a period of 3 months from July 2020 to September 2020. In our study, all 79 patients had complete blood counts performed at the time of admission. Complete blood count was repeated during the hospital stay for all severe cases. The data which provided information on the age and gender of each patient were obtained from the Laboratory Information System (LIS) of the hospital. Results: The mean age of our study group was 46.05 years. Out of 79 cases, lymphopenia was seen in 16.5% with five patients presenting with severe lymphopenia (<0.5 × 109 /L). All the patients that required ICU care presented with moderate to severe lymphopenia. The patients in the ICU setting showed significant neutrophilia (mean 14.16 × 109 /L) on follow-up complete blood count. Thrombocytopenia was observed in 35.3% of cases. It was observed that the mean neutrophil– lymphocyte ratio was higher in ICU admitted patients as compared to the non-ICU admitted patients. Among the ICU patients, 80% showed a neutrophil–lymphocyte ratio above the baseline cutoff (3.1). A wide array of morphological changes were observed in the peripheral blood smear including toxic-like granules in neutrophils, fetus-like C-shaped nucleus, lymphoplasmacytoid cells, bizarre cells, and apoptotic cells. Conclusion: The study highlights that at the time of admission older age, decreased lymphocyte count, and raised neutrophil–lymphocyte ratio were closely associated with ICU admissions. Also, the morphological changes in peripheral blood film reveal atypical changes predominantly in the white blood cell (WBC) lineage.

Imaging Characteristics of Carotid Plaques by Doppler Ultrasonography and Magnetic Resonance Imaging in Ischemic Stroke: A Comparative Analysis

Background: Carotid plaques contribute a significant cause of stroke and transient ischemic attacks together with long term disability worldwide. About 20-30% of cerebral infarction has been correlated with carotid atherosclerotic plaque and artery stenosis. The characterization of carotid artery plaque presents an opportunity to quantify patients with risk of cerebrovascular events and may be used to improve the therapeutic decision-making process such as carotid endarterectomy or angioplasty or stent placement. This study attempted to evaluate the imaging characteristics of carotid plaques using ultrasonography with Magnetic Resonance Imaging correlation and predict the risk of plaque rupture based on plaque enhancement characteristics as a surrogate marker. Materials and methods: Aim of the study was to evaluate and compare morphological characteristics of carotid plaques with Doppler ultrasonography and MRI and to predict plaque enhancement characteristics on MRI as a potential surrogate marker for plaque rupture leading to recurrent strokes. The present study evaluated 113 patients (65 males and 48 females) with stroke and transient ischemic attacks with ultrasound documented carotid plaques. These cases underwent Doppler evaluation of the carotid plaques and contrast enhanced MRI on the same day. The plaque morphology was evaluated both in the longitudinal as well as the transverse axis, and the stenosis was calculated based on the pulsed- wave Doppler evaluation of blood flow velocity as well as the area and diameter of the stenosis together with the signal and enhancement characteristics of the carotid plaques on MRI. The carotid artery at the region of maximal intimal thickness was evaluated for maximal area stenosis and diameter stenosis. The area stenosis was calculated as percentage stenosis in axial sections at the site of maximal thickness of the plaque. Results: The maximum incidence of carotid plaques was noted in the 61-80 years age group. The incidence was maximal at 71-80 years of age. Out of the 113 lesions, 65 (57.5%) were in men and 48 (42.4%) were in women. 44(38.9%) lesions were in patients who presented with TIA, while 69 (61.06%) presented with Ischemic stroke. 67 (59.29%) lesions were found on the left side and 46 (40.7%) on the right side. 67(59.3 %) lesions were found in the carotid bulb. The intimal thickness ranged from 1.1 mm to 5.6 mm with a mean of 2.97 mm. The range of stenosis was from 0% to 100%. Heterogeneous plaques were associated with symptomatic lesions in 76.2 % and homogeneous plaques were seen in 23.8%. The incidence of plaque calcification was inversely proportional to symptomatic plaques. Only 47.2 % of patients showed concordance between US and MRI with regard to homogeneity of the plaque. T2 weighted MR imaging of exvivo atherosclerotic plaques aided in the detection and evaluation of fibrous caps. 39 (34.1%) patients were given a gadolinium-based contrast agents, out of which 19 (48.7 %) did not show enhancement and 20 (51.2%) showed enhancement of the carotid plaque tissue. Doppler showed abnormalities in 29 patients (61.7%), whereas in MRA it is 18 patients (38.2 %), p value = < 0.004* in cases with less than 50% stenosis (n=47). In cases with 50-69% stenosis (n=29), doppler showed abnormalities in 19 patients (65.5%) whereas in MRA it was (34.4 %); P value was 0.431, The difference was not found to be statistically significant. While as in cases with 70-90% stenosis (n=37), MRA showed abnormalities in 25 patients (67.5%) whereas Doppler showed it in 12 (32.4%); P value was 0.017. Calcification was seen in 22 patients which appeared as hypointense focus on T1, T2, and TOF images. The heterogeneous lesions were better visualized on ultrasound compared to MRI. Conclusion: Ultrasound is a more sensitive modality than MRI for plaque size < 1.5 mm and a better tool in assessing the plaque characteristics when the area of stenosis is less than 50%. Hence, ultrasound is better as a screening tool. The homogenous lesions on ultrasound appeared homogenous on MRI with the plaque content of fat. The heterogeneous plaque on ultrasound, however, did not correlate with MRI. Enhancement of carotid plaque tissue, which implies vascular wall inflammation, is a marker of vulnerable plaque. MRA has a better discriminatory power compared with duplex ultrasonography in detecting 70-90% stenosis

Clinico-epidemiological profile of enteric fever at a peripheral health centre in Kashmir valley

Enteric fever commonly known as typhoid fever remains endemic in many developing countries with an estimate of more than 26.9 million cases recorded annually with 1% associated deaths. We conducted a study to evaluate clinico-epidemiological profile of enteric fever in a peripheral hospital of Kashmir North India. This was a hospital based cross sectional study conducted over a period of one year including a total of 100 patients between 1-12 years of age. All children who have documented fever of more than one week duration with widal titres of >160 were included in the study. Among 100 patients included in the study 94% had fever of >1 week of duration, 68% and 50% had anorexia and vomiting respectively. Diarrhea was present in 28% of the study population with constipation in 10%. 28% had hepatomegaly on examination while as 12% had spleenomegaly. Headache was present in 17% of population. Our study concluded that enteric fever continues to be a significant cause of morbidity and mortality in developing nations especially in the rural population. Poor hygiene, lack of proper community education, limited healthy care facilities and negligible typhoid vaccination are the main concerns which need to be addressed on priority to decrease the disease burden.

Interzygomatic and Intercanthal width - Gender determination methods in forensic dentistry

Background: Personal identification is a subtle perception and often one of the most significant priorities in the investigation of criminal cases, mass disasters, and in forensic concerns. Gender determination is one of the important parameters in forensic identification. The study of anthropometric characteristics is of fundamental importance to solve problems related to such cases. Aim: This study aimed to determine gender using physical anthropometric methods like interzygomatic and intercanthal width. Materials and Methods: A cross-sectional study was conducted among 60 individuals (30 males and 30 females) in the department of Oral Pathology, Government Dental College and Hospital Srinagar. Interzygomatic width, and intercanthal width was determined using a digital sliding caliper. All the measurements were taken twice. The final value was the average of the two obtained values. Results: There was significantly higher mean interzygomatic and intercanthal width in males as compared to females. Conclusion: Interzygomatic and intercanthal measurements may serve as diagnostic markers for gender identification in forensic applications like mass disasters.

FACTORS RESPONSIBLE FOR DELAYS IN SEEKING DIAGNOSIS AND TREATMENT OF PULMONARY TUBERCULOSIS IN A TERTIARY CARE HOSPITAL OF DEHRADUN– A CROSS SECTIONAL STUDY

Tuberculosis (TB) is an infectious disease, in which Mycobacterium tuberculosis is the causative agent. When a person progresses from infection to disease, they may not experience obvious symptoms for a long time, (e.g cough, fever, hemoptysis, weight loss etc). This might lead to delay in diagnosis and treatment seeking. One of the components of timely diagnosis and treatment of tuberculosis is estimating the delay in diagnosis of TB and assessing the factors contributing to the delay. To Aim and Objectives: describe the delays in the diagnosis and treatment of pulmonary Tuberculosis and to study the socio demographic determinants responsible for the same. A time bound institution based study was conducted in a tertiary care Methodology: hospital in department of pulmonary medicine. A total of 50 patients were included in the study by means of total enumeration. diagnosti Result: c and consultation delays were the most common cause of delays in seeking diagnosis and treatment of Pulmonary Tuberculosis.

Prevalence and Echocardiographic Predictors of Left Atrial Appendage Inactivity in Patients of Mitral Stenosis

Background: Mitral stenosis (MS) is a common valvular heart disease. Thromboembolism is one of the most serious consequences of mitral stenosis, particularly when it is accompanied with atrial fibrillation (AF). When linked with Left atrial appendage inactivity (LAAI), patients with sinus rhythm (SR) are also at risk for this condition. In mitral stenosis, LAA inactivity determined by S-wave is an independent predictor of thromboembolism. The aim of the study was to evaluate the Prevalence and Echocardiographic Predictors of Left Atrial Appendage inactivity in patients of Mitral Stenosis.Material & Methods:Sixty MS patients were evaluated by transthoracic echocardiography (TTE) and all patients underwent transesophageal echocardiography (TEE). The annular systolic (S-wave) and diastolic (Em- and Am-waves) velocities were recorded by tissue Doppler imaging (TDI). LAA inactivity was defined as LAA emptying velocity <25 cm/second determined by pulse wave Doppler at the junction of LA & LAA (TEE). Patients were divided into three groups; group A I (n = 18). Sinus rhythm (SR) and LAA emptying velocity ?25 cm/sec, group A II (n -22): SR and LAA emptying velocity <25cm/sec and group B (n = 20): atrial fibrillation.Results:Thrombus was detected in 14 patients and spontaneous echo contrast (SEC) was detected in 43 patients. Both S-wave and peak LAA emptying velocities were decreasing, while SEC frequency and density were increasing from group A to group B. There was a positive correlation between LAA emptying vs. S-wave and LAA emptying vs. Am velocities (p < 0.001, r= 0.708 and p<0.001, r=0.495). Multivariate regression analysis showed that only S-wave is the independent predictor of inactive LAA (p = 0.001, odds ratio = 0.133, 95% Cl =0.032-0.556). In patients with SR, the cutoff value of S-wave was 10 cm/sec for the prediction of the presence of inactive LAA (sensitivity: 92.3%, specificity: 95.3%).Conclusions:In individuals with severe mitral stenosis in sinus rhythm, there is a significant prevalence of left atrial appendage inactivity. The mean pressure gradient across the mitral valve, as well as S-wave are independent predictors of left atrial appendage inactivity. Inactivity of the left atrial appendage is an independent predictor of left atrial/left atrial appendage smoke and associated thrombus.

Kashmiri refugees at the verge of hepatitis B and C epidemic in the State of Azad Jammu and Kashmir, Pakistan

ABSTRACT OBJECTIVE To determine the seroprevalence of hepatitis B and C among immigrants residing refugee camps in Muzaffarabad, Azad Kashmir, Pakistan, and to identify possible risk factors for hepatitis B virus (HBV) and hepatitis C virus (HCV) transmission. METHODS Around 1,225 individuals inhabiting Muzaffarabad refugee camps, participated in the study. A qualitative Immuno-Chromatographic Technique was used for initial screening and PCR test was used for detection of HBV and HCV in participants. The major risk factors for HBV and HCV transmission were assessed using a questionnaire approach. RESULTS Around 86 (7.0%) individuals were observed for hepatitis B surface antigen (HBsAg) presence, and 215 (17.5%) individuals were found positive for Anti-HCV. Only 32 (2.6%) individuals were confirmed for HBV DNA and 126 (10.3%) individuals were positive for HCV RNA after PCR. Demographically, both HBsAg and Anti-HCV were found more prevalent in female (4.4% HBsAg and 10.8% Anti-HCV) population as compared to male (2.6% HBsAg and 6.7% Anti-HCV) population. Surprisingly, the HBsAg (23.5%) and Anti-HCV (41.1%) appeared to be more frequent in the age group 62-75 years. Previous history of hepatitis in the family (p < 0.0001), blood transfusion (p = 0.0197) dental treatment (p < 0.0001) and tattooing or piercing on any part of the body (p = 0.0028) were assessed as significant risk factors in HBV and HCV transmission. CONCLUSIONS Presence of 7.0% HBsAg and 17.5% Anti-HCV in a small fragment of the migrant population cannot be overlooked. Lack of awareness among people and negligence of health department could escalate the situation.

CO1-Based DNA barcoding for assessing diversity of Pteropus giganteus from the state of Azad Jammu Kashmir, Pakistan / Código de barras de DNA à base de CO1 para avaliar a diversidade de Pteropus giganteus do estado de Azad Jammu e Caxemira, Paquistão

Abstract The flying fox (Pteropus giganteus) also familiar with the name of the greater Indian fruit Bat belongs to the order Chiroptera and family Pteropodidae. Current research emphasis on the DNA barcoding of P. giganteus in Azad Jammu Kashmir. Bat sequences were amplified and PCR products were sequenced and examined by bioinformatics software. Congeneric and conspecific, nucleotide composition and K2P nucleotide deviation, haplotype diversity and the number of haplotypes were estimated. The analysis showed that all of the five studied samples of P. giganteus had low G contents (G 19.8%) than C (27.8%), A (25.1%) and T (27.3%) contents. The calculated haplotype diversity was 0.60% and the mean intraspecific K2P distance was 0.001% having a high number of transitional substitutions. The study suggested that P. giganteus (R=0.00) do not deviate from the neutral evolution. It was determined from the conclusion that this mtDNA gene is a better marker for identification of Bat species than nuclear genes due to its distinctive characteristics and may serve as a landmark for the identification of interconnected species at the molecular level and in the determination of population genetics.

Resumo A raposa-voadora (Pteropus giganteus), também conhecida como morcego indiano, pertence à ordem dos Chiroptera e à família Pteropodidae. A presente pesquisa dá ênfase ao código de barras de DNA de P. giganteus em Azad Jammu e Caxemira. Sequências genéticas dos morcegos foram amplificadas, e os produtos de PCR foram sequenciados e examinados por software de bioinformática. De espécies congenérica e coespecífica, foram estimados composição nucleotídica e desvio de nucleotídeos K2P, diversidade de haplótipos e número de haplótipos. A análise mostrou que todas as cinco amostras estudadas de P. giganteus apresentaram baixos teores de G (19,8%) em comparação com C (27,8%), A (25,1%) e T (27,3%). A diversidade de haplótipos calculada foi de 0,60%, e a distância média intraespecífica de K2P foi de 0,001%, com um elevado número de substituições transicionais. O estudo sugeriu que P. giganteus (R = 0,00) não se desviou da evolução neutra. É possível concluir que o gene mtDNA é um marcador favorável para identificação de espécies de morcegos do que genes nucleares por causa de suas características distintivas e pode servir como um marco para a identificação de espécies interconectadas em nível molecular e para a determinação genética de populações.

Punica granatum and amygdalin extracts plus cobalamin combined with albendazole reduce larval burden and myositis in experimental trichinosis / Extratos de Punica granatum e amígdalina mais cobalamina combinado com albendazol reduzem a carga larvar e a miosite na triquinose experimental

Abstract Trichinellosis is a zoonosis results from eating raw or semi-cooked meat of infected animals. Medicinal plants have been used lately as alternatives and/or combined therapies to resolve some drawbacks of the current regimens. This work analyzed the effect of albendazole monotherapy on Trichinella spiralis experimental infection (group A), in comparison to P. granatum and amygdalin extracts +cobalamin (group B), plus its combination with albendazole (group C). The study revealed that the extracts alone or combined with albendazole had an inferior effect to albendazole monotherapy regarding number of adult worms (40.83 ±3.82, 18.67 ±1.86 and 16.83 ±2.32, respectively). However, their effect was more obvious in muscle phase combined with albendazole, achieving the lower number of larvae/mL tissue homogenate (22.33 ±3.27 in comparison to 39.67 ±2.58 achieved by albendazole monotherapy). The extracts exerted a significant immunomodulatory effect by reducing the local CD4+ expression in the intestine as well as in muscle phase (1.15 ±0.25 and 3.80 ±0.65 in comparison to 4.97 ±0.37 and 12.20 ±0.87 with albendazole monotherapy, respectively). So, these extracts improved the therapeutic efficacy of albendazole, specifically in muscle phase and counteracted the inflammatory reaction caused by albendazole monotherapy, thus extensively alleviating the resulting myositis.

Resumo Trichinellosis é uma zoonose resultante da ingestão de carne crua ou semicozida de animais infectados. As plantas medicinais têm sido usadas, ultimamente, como alternativas e/ou terapias combinadas, para resolver algumas desvantagens dos regimes atuais. Este trabalho analisou o efeito da monoterapia albendazole na infecção experimental por Trichinella spiralis (grupo A), em comparação com extratos de P. granatum e amígdalina +cobalamina (grupo B), além de sua combinação com albendazol (grupo C). O estudo revelou que os extratos sozinho ou combinado com albendazol teve efeito inferior à monoterapia albendazol em relação ao número de vermes adultos (40,83 ±3,82, 18,67 ±1,86 e 16,83 ±2,32, respectivamente). No entanto, seu efeito foi mais óbvio na fase muscular combinado com o albendazol, alcançando o menor número de larvas/mL homogeneizado de tecido (22,33 ±3,27 em comparação com 39,67 ±2,58 obtidos pela monoterapia albendazol). Os extratos exerceram um efeito imunomodulatório significativo, ao reduzir a expressão local CD4+ no intestino, bem como na fase muscular (1,15 ±0,25 e 3,80 ±0,65 em comparação com 4,97 ±0,37 e 12,20 ±0,87 com monoterapia albendazol, respectivamente). Assim, esses extratos melhoraram a eficácia terapêutica do albendazol, especificamente na fase muscular e neutralizaram a reação inflamatória causada pela monoterapia albendazol, aliviando extensivamente a miosite resultante.

Denosumab can be used successfully as a bridge to surgery in patients with severe hypercalcemia due to primary hyperparathyroidism

SUMMARY Severe hypercalcemia is a medical emergency that requires immediate and aggressive management. Primary hyperparathyroidism (PHPT) often causes severe hypercalcemia. Volume resuscitation, parenteral salmon calcitonin, and administration of intravenous bisphosphonates are common measures used to stabilize patients. However, the use of these measures is inadequate in several patients and may even be contraindicated in individuals with renal insufficiency or severe systemic illness. This study demonstrated the efficacy and safety of denosumab in patients with severe hypercalcemia due to PHPT, when immediate surgery was not feasible. We present four patients with severe hypercalcemia due to PHPT. Immediate surgery was not feasible because the patients had severe systemic illness, such as seizures and altered sensorium (case 1); acute severe pancreatitis (cases 2 and 3); or coronavirus disease 2019 pneumonia (case 4). Intravenous normal saline and parenteral salmon calcitonin were inadequate for controlling hypercalcemia. Intravenous bisphosphonates were avoided because of severe systemic illness in all cases and impaired renal function in three cases. Denosumab was administered to control hypercalcemia and allow the stabilization of patients for definitive surgical management. Following denosumab administration, serum calcium levels normalized, and general condition improved in all patients. Three patients underwent parathyroidectomy after two weeks and another patient after eight weeks. The use of denosumab for the management of severe hypercalcemia due to PHPT is efficacious and safe in patients when immediate surgical management is not feasible due to severe systemic illness.

Attitude and perception towards vaccination against poliomyelitis in Peshawar, Pakistan

ABSTRACT OBJECTIVE: This research aimed to quantitatively assess the general public's awareness, attitude and perception of polio and its vaccination in Peshawar KPK, Pakistan. METHODS: We conducted a survey-based study to understand the surge in polio cases from 2015 to 2019 in the Peshawar city of the Khyber Pakhtunkhwa (KPK), Pakistan. A pre-tested questionnaire-based study was conducted in 2019 to assess the attitude and general perception of residents of Peshawar KPK towards polio vaccination. RESULTS: Out of 241 country-wide polio cases, 63 (26.1%) polio cases were reported in Peshawar city from 2015-2019. The questionnaire revealed that individuals between 18-30 years of age had sufficient knowledge (65.1%) about polio. Male and female participants had equal awareness (~ 43%). Participants with higher education (45.9%), those with better financial status (49.5%), individuals with children < 5 years of age (46.4%), and those who had experience of a polio patient (63.1%) had better knowledge. Participants inhabiting the central city were better aware (50.5%) of polio than individuals living in the outskirts. CONCLUSION: The data indicated that poor knowledge and negative attitudes of people towards polio vaccination are the main causes of the polio eradication program's failure. Moreover, religious beliefs, unchecked migration between the Pak-Afghan border, and lack of knowledge about polio vaccination are identified as critical barriers to polio eradication.

Prevalence and clinical correlates of psychiatric morbidity among caregivers of patients attending a psychiatric hospital in North India

Background: Consequent to the high prevalence of psychiatric disorders in present day world, their caregivers form an important group in the public health. Research on the physical and psychological well-being of caregivers is being carried worldwide with varied results. Psychological health of these caregivers is usually ignored both by these persons themselves and the health-care providers. The objective of the study was to screen for psychiatric morbidity among caregivers of patients attending a psychiatric hospital in North India, and to study the clinical correlates of the same.Methods: A total of 205 patients and their caregivers were consecutively recruited over a one month period. Sociodemographic and clinical information of patients was obtained either from the hospital records or from the caregiver. Scoring of the patient’s global assessment of functioning (GAF) was done by clinicians. The caregivers were administered a sociodemographic questionnaire, general health questionnaire (GHQ-12) and Zarit Burden interview. The presence of psychiatric morbidity was confirmed by a consultant psychiatrist.Results: Among the caregivers, 32.2% had GHQ scores of 3 and above. Majority of caregivers in this study were females (59.0%) while as majority of the patients were males (61.9%). Factors associated with psychiatric morbidity among caregivers include the high level of subjective burden of care, low level of functioning, and comorbid medical and psychiatric conditions.Conclusions: The study reveals a high level of psychiatric morbidity among the caregivers of patients with mental health problems.

Evaluation of chemopreventive and chemotherapeutic effect of Artemisia vulgaris extract against diethylnitrosamine induced hepatocellular carcinogenesis in Balb C mice / Avaliação dos efeitos quimiopreventivo e quimioterápico do extrato de Artemisia vulgaris contra carcinogênese hepatocelular induzida por dietilnitrosamina em camundongos Balb C

The main objective of current study was to investigate the chemopreventive and chemotherapeutic activity of Artemisia vulgaris extract on diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Diethylnitrosoamine (DEN: 0.9%) was prepared to induce hepatocarcinoma in Balb C mice. The extract Artemisia vulgaris (AV) was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 l/mg), group 2 (N=14) received diethylnitrosoamine (3.5 l/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received only plant extract (AV: 150 mg/kg (Body weight) once in a week, while group 4 (N=7) was given in combination of diethylnitrosoamine (3.5 l/mg) and plant extract (AV: 150 mg/kg (body weight). After eight weeks of DEN administration, mice of group 2 were divided into two subgroups containing seven mice each; subgroup 1 was sacrificed while subgroup 2 was treated with plant extract only (150 mg/kg (body weight)) once in a week for eight consecutive weeks. The DEN injected mice significant decline in levels of albumin with concomitant significant elevations such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alpha feto protein, gamma glutamyl transferase, 5 nucleotidase, glucose-6-phosphate dehydrogenase and bilirubin. The administration of A. vulgaris significantly decreased the DEN induced hepatotoxicity. Present study revealed the potential anti-cancerous nature of Artemisia vulgaris, both in case of chemopreventive and post-treatment of A. vulgaris. Further studies are needed to explore the mechanism of prevention and therapy.

O objetivo principal do presente estudo foi investigar as atividades quimiopreventiva e quimioterápica do extrato de Artemisia vulgaris em hepatocarcinogênese induzida por dietilnitrosoamina (DEN) em camundongos Balb C. Dietilnitrosoamina (DEN: 0,9%) foi preparada para induzir hepatocarcinoma em camundongos da linhagem Balb C. O extrato de A. vulgaris (AV) foi preparado pela técnica de maceração. Os camundongos foram classificados em quatro grupos conforme os seguintes: grupo 1, grupo controle (N=7) recebeu solução salina (3,5 µl/mg); grupo 2 (N=14) recebeu dietilnitrosoamina (3,5 µl/mg) por via intraperitoneal uma vez por semana durante oito semanas consecutivas; grupo 3 (N=7) recebeu apenas o extrato vegetal (AV: 150 mg/kg (peso corporal) uma vez por semana; enquanto no grupo 4 (N=7) foi administrado uma combinação de dietilnitrosoamina (3,5 l/mg) com extrato vegetal (AV: 150 mg/kg (peso corporal). Após oito semanas de administração de DEN, os camundongos do grupo 2 foram divididos em dois subgrupos, contendo sete camundongos cada um; no subgrupo 1, os animais foram sacrificados, enquanto no subgrupo 2, os animais foram tratados apenas com extrato vegetal (150 mg/kg (peso corporal)) uma vez por semana durante oito semanas consecutivas. Os camundongos nos quais foram injetados DEN apresentaram declínio significativo nos níveis de albumina, mas elevações significativas concomitantes de: aspartato aminotransferase, alanina aminotransferase, lactato desidrogenase, alfa-fetoproteína, gama-glutamiltransferase, 5 nucleotidase, glicose-6-fosfato desidrogenase e bilirrubina. A administração de A. vulgaris diminuiu significativamente a hepatotoxicidade induzida pelo DEN. O presente estudo apresentou a potencialidade anticancerosa da A. vulgaris, tanto nos casos de quimioprevenção quanto no pós-tratamento da A. vulgaris. Mais estudos são necessários para explorar o mecanismo de prevenção e a terapia.

Assessment and incidence of fish associated bacterial pathogens at hatcheries of Azad Kashmir, Pakistan / Avaliação e incidência de patógenos bacterianos associados a peixes em incubadoras da Caxemira de Azad, Paquistão

Abstract Fish is the most indispensable source of proteins for individuals and have high nutritional value. On the other hand, the fish culturing raised issues of fish health due to close contact between the aquatic environment and the fish pathogens. So, the aim of the current study was to identify the bacterial pathogens and screen the injured Rainbow trout rearing in different trout hatcheries run under fisheries department of the government of Azad Jammu and Kashmir, Pakistan. Seven bacterial pathogens such as Shigella flexneri, Enterobacter amnigenus, Salmonella Typhimurium, Serratia odorifera, Pseudomonas aeruginosa, Streptococcus pyogenes, and Bacillus cereus were isolated and identified. Results revealed that the injury of fish specimens was due to overcrowding. Instead of rainbow coloration, specimens have darker black in color. The water of ponds was not clean and clear and such conditions was because of the greater quantity of feed thrown in the water. It was concluded that poor hygienic water condition and overloading allowed the opportunistic bacterial contaminations to succeed which cause a serious threat to hatcheries.

Resumo O peixe é a fonte mais indispensável de proteínas para os indivíduos e tem alto valor nutricional. Por outro lado, a cultura dos peixes levantou questões sobre a saúde dos peixes devido ao próximo contato entre o ambiente aquático e os agentes patogênicos desses peixes. Assim, o objetivo do presente estudo foi identificar os patógenos bacterianos e rastrear a criação da truta arco-íris que apresentou lesões em diferentes incubadoras de trutas, com supervisão do departamento de pesca do governo de Azad Jammu e Caxemira, Paquistão. Sete patógenos bacterianos foram isolados e identificados, tais como: Shigella flexneri, Enterobacter amnigenus, Salmonella typhimurium, Serratia odorifera, Pseudomonas aeruginosa, Streptococcus pyogenes e Bacillus cereus. Os resultados revelaram que a lesão de espécimes de peixes foi devido à superlotação. Em vez da coloração do arco-íris, os espécimes tiveram uma coloração preta mais escura. A água das lagoas não era limpa e nem clara, e tais condições ocorreram devido a maior quantidade de alimento lançada na água. Concluiu-se que a precária condição higiênica da água e também a sobrecarga permitiram que as contaminações bacterianas oportunistas fossem bem-sucedidas, causando séria ameaça às incubadoras.

Evaluation of chemopreventive and chemotherapeutic effect of Artemisia vulgaris extract against diethylnitrosamine induced hepatocellular carcinogenesis in Balb C mice / Avaliação dos efeitos quimiopreventivo e quimioterápico do extrato de Artemisia vulgaris contra carcinogênese hepatocelular induzida por dietilnitrosamina em camundongos Balb C

Abstract The main objective of current study was to investigate the chemopreventive and chemotherapeutic activity of Artemisia vulgaris extract on diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Diethylnitrosoamine (DEN: 0.9%) was prepared to induce hepatocarcinoma in Balb C mice. The extract Artemisia vulgaris (AV) was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 μl/mg), group 2 (N=14) received diethylnitrosoamine (3.5 μl/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received only plant extract (AV: 150 mg/kg (Body weight) once in a week, while group 4 (N=7) was given in combination of diethylnitrosoamine (3.5 μl/mg) and plant extract (AV: 150 mg/kg (body weight). After eight weeks of DEN administration, mice of group 2 were divided into two subgroups containing seven mice each; subgroup 1 was sacrificed while subgroup 2 was treated with plant extract only (150 mg/kg (body weight)) once in a week for eight consecutive weeks. The DEN injected mice significant decline in levels of albumin with concomitant significant elevations such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alpha feto protein, gamma glutamyl transferase, 5 nucleotidase, glucose-6-phosphate dehydrogenase and bilirubin. The administration of A. vulgaris significantly decreased the DEN induced hepatotoxicity. Present study revealed the potential anti-cancerous nature of Artemisia vulgaris, both in case of chemopreventive and post-treatment of A. vulgaris. Further studies are needed to explore the mechanism of prevention and therapy.

Resumo O objetivo principal do presente estudo foi investigar as atividades quimiopreventiva e quimioterápica do extrato de Artemisia vulgaris em hepatocarcinogênese induzida por dietilnitrosoamina (DEN) em camundongos Balb C. Dietilnitrosoamina (DEN: 0,9%) foi preparada para induzir hepatocarcinoma em camundongos da linhagem Balb C. O extrato de A. vulgaris (AV) foi preparado pela técnica de maceração. Os camundongos foram classificados em quatro grupos conforme os seguintes: grupo 1, grupo controle (N=7) recebeu solução salina (3,5 µl/mg); grupo 2 (N=14) recebeu dietilnitrosoamina (3,5 µl/mg) por via intraperitoneal uma vez por semana durante oito semanas consecutivas; grupo 3 (N=7) recebeu apenas o extrato vegetal (AV: 150 mg/kg (peso corporal) uma vez por semana; enquanto no grupo 4 (N=7) foi administrado uma combinação de dietilnitrosoamina (3,5 μl/mg) com extrato vegetal (AV: 150 mg/kg (peso corporal). Após oito semanas de administração de DEN, os camundongos do grupo 2 foram divididos em dois subgrupos, contendo sete camundongos cada um; no subgrupo 1, os animais foram sacrificados, enquanto no subgrupo 2, os animais foram tratados apenas com extrato vegetal (150 mg/kg (peso corporal)) uma vez por semana durante oito semanas consecutivas. Os camundongos nos quais foram injetados DEN apresentaram declínio significativo nos níveis de albumina, mas elevações significativas concomitantes de: aspartato aminotransferase, alanina aminotransferase, lactato desidrogenase, alfa-fetoproteína, gama-glutamiltransferase, 5' nucleotidase, glicose-6-fosfato desidrogenase e bilirrubina. A administração de A. vulgaris diminuiu significativamente a hepatotoxicidade induzida pelo DEN. O presente estudo apresentou a potencialidade anticancerosa da A. vulgaris, tanto nos casos de quimioprevenção quanto no pós-tratamento da A. vulgaris. Mais estudos são necessários para explorar o mecanismo de prevenção e a terapia.