Grave Form Research Articles

Observation of Unexplained Cases of Unilateral Upper Eyelid Retraction from Idiopathic Inflammation or an Atypical Form of Graves' Orbitopathy.

We observed cases of unilateral upper eyelid retraction (UER) with unclear pathogenesis, where a definitive diagnosis of Graves' orbitopathy (GO) could not be made and other pathologies were ruled out. The aim is to present patients' findings, discuss possible underlying mechanisms, and to describe diagnostic testing and therapeutic approaches. Patients were retrospectively analyzed who presented to the Department of Ophthalmology of LMU Munich between 2016 and 2021 without a definitive diagnosis of GO or other pathological causes. Thirteen patients with unexplained UER were included; all showed thickening of the levator complex in imaging. When biopsy was performed, no malignancy could be detected. Therapeutic strategies included oral steroids and surgical upper eyelid blepharotomy. As regards to pathogenesis, in 7/13 patients, a condition of idiopathic UER due to an idiopathic inflammatory response can be postulated rather than a variant of GO.

Impact of maternal education on the development of severe acute malnourished children

Background: Severe acute malnutrition (SAM) is a grave form of undernutrition that has been recognized as a medical and social disorder. Various factors contribute to the development of SAM, but the impact of maternal education on the nutritional status and development of the child is of paramount importance since focused interventions in this aspect can yield promising results. Aims and Objectives: The aims and objectives of the study are to assess the impact of maternal education on the development of children with SAM. Materials and Methods: A total of 125 SAM children in the age group 12–30 months were enrolled in this prospective observational study from among those admitted to the nutritional rehabilitation center of a tertiary care center in central India. The developmental status of SAM children was assessed using the Developmental Assessment Scale of Indian Infants. The association of maternal education with the development of SAM children was analyzed. Results: Overall developmental delay was observed in 44.8% of SAM children, whereas motor and mental development delay was noted in 45.6% and 44% of SAM children. The maternal education level was significantly associated with the overall development of the SAM child. (P=0.043 for motor development, P=0.017 for mental development, P=0.023 for motor developmental delay). Conclusion: Maternal education plays a key role in improving the developmental status of SAM children, who are more prone to developmental delays across various domains. Efforts toward enhancing maternal education, especially knowledge regarding child nutrition and development, can reduce the incidence and improve the management of SAM in children.

The noble cause of medicine – fact or fallacy?

The aim of the article is threefold: to argue and motivate that unnecessary surgery is a worldwide phenomenon, that it exposes patients to unwarranted risks and that patients should actively participate in decision-making and take a shared responsibility to protect their interests. There is a firm belief that the enterprise of medicine is something of value – both intrinsically because being healthy is good and instrumentally since being healthy allows us to do what we wish to, to attain happiness and to live valuable lives. However, this can only hold if treatment is justified in terms of accepted evidence-based criteria. Imperative for all forms of treatment, including costly and invasive investigations, this is particularly true for surgical interventions because no surgery is without risk. Surgery performed outside of the norms of accepted indications constitutes a grave form of assault. Medicine is a noble cause if we stick to the rules and help each other to do so. As professionals, our most fundamental regulation is by ourselves.

Stereotactic hematoma puncture and drainage for primary pontine hemorrhage: Clinical outcomes and predictive model

Primary pontine hemorrhage (PPH) is a particularly grave form of hemorrhagic stroke, characterized by its significant mortality rate. stereotactic hematoma puncture and drainage is a procedure that has been shown to improve the prognosis of patients with PPH. However, there are currently no established criteria for selecting patients for this procedure. We contrasted the clinical outcomes of PPH patients treated with stereotactic hematoma puncture and drainage with those who received conservative treatment in this study. We conducted logistic regression analysis to identify the risk factors associated with postoperative mortality. A mortality risk nomogram was then constructed using these risk factors. A total of 127 conservatively treated patients and 96 patients who underwent stereotactic hematoma puncture and drainage were included in this study. In the surgical group, the 30-day mortality rate stood at 28.1%, significantly lower than the 43.3% observed in the control group (p = 0.02). Age, along with the Glasgow Coma Scale (GCS) score and hematoma size, were identified as independent risk factors associated with death within 30 days post-surgery. The mortality risk nomogram was well calibrated and discriminatory, with a c-index of 0.878 (95% CI 0.80–0.95) as validated by bootstrapping, and a c-index of 0.849. This study provides a predictive model for selecting patients who are most likely to benefit from stereotactic hematoma puncture and drainage. The results of this study could be helpful to neurosurgeons in their decision-making process. However, further external validation is necessary to confirm these findings.

New Perspectives on Child and Infant Burial in Britain (100 b.c.e.–c.e. 200)

AbstractFocusing on a period of social shift, from the Late Iron Age to the early Roman period (100 b.c.e.–c.e. 200), this paper examines how the value of juvenile (under 13-year-old) bodies changed. In exploring the fluctuation in burial numbers alongside the altering forms of juvenile graves, the paper details the ways in which children (1- to 12-year-olds) and infants (younger than 1 year in age) were identified in death, as well as the longevity of these identifications. It is argued that juveniles are less common than they should be in the funerary record. Given that this relative absence of juvenile burial was clearly socially mandated, the emphasis here is on better contextualising and interrogating the sporadic presence and deposition of such burials.

Comparison of the efficacy of two different glucocorticoid regimens for treatment of active moderate-to-severe Graves' orbitopathy.

Intravenous glucocorticoids (GCs) are the mainstay of treatment for severe forms of Graves' orbitopathy (GO). Our aim was to assess the effectiveness and safety of a modified monthly regimen (mMR) and to compare them with those of the established weekly regimen (WR). This was a prospective non-randomized single-center study involving 62 patients, divided into two therapeutic groups depending on their referral time. Thirty-one subjects, admitted in the period 2017-2018, were treated with mMR, total dose-5.5g, with intake of oral GCs after completion of intravenous infusions. Thirty subjects, who were referred in the period 2019-2020, were treated with WR, total dose-4.5g One patient refused to be part of the WR group and was treated with mMR. Eye status and therapeutic response were evaluated on the 1st, 3rd and 6th months, quality of life-at 3rd and 6th month. At 1st month and 3rd month, there was no significant difference in the therapeutic response between the two groups. At 3rd month, the proportion of patients with improvement in soft tissue manifestations and subjective complaints was significantly higher in mMR group (65.6% vs. 40% and 81.3% vs. 46.7%, respectively) and the same manifestations were of significantly milder degree. At 3rd month, significant improvement in quality of life was found without significant difference between the two groups. At 6th month, worsening of GO occurred in 3 patients from WR group, while in 5 patients from mMR group further improvement was found. The two GC regimens have comparable efficacy with small differences in the time of onset of the effect and its duration, as well as in the effectiveness on some ocular manifestations. Trial registration number NCT05793359/29.03.2023, retrospectively registered..

Role of MRCP in Patients with Jaundice When Biliary Tree Is Normal on Previous Imaging

Background Obstructive jaundice is one of the most frequent and grave form of hepatobiliary disease. It is important for treatment planning to detect level and cause of obstruction. Aim of the Work To assess the role of MRCP in patients presented with jaundice, right hypochondrial pain with the absence of dilated biliary system by ultrasound. Patients and Methods This was cross sectional study that included 38 patients who presented with obstructive jaundice or right hypochondrial pain with normal biliary system by ultrasound referred to the Radio diagnosis Department for MRCP. Results MRCP has high sensitivity reaching 100% and high specificity reaching 93.33% in gall bladder pathology and high specificity 100% in biliary and pancreatic pathology in comparison to ultrasound. Conclusion if there is high clinical suspicion of ductal pathology when patient presented by jaundice or right hypochondrial pain with abnormal liver function tests despite normal biliary tree by ultrasound, an MRCP examination should be strongly considered as next imaging modality of choice

Indigenous Community-Based Cultural Tourism Communication

Kampung Adat Ratenggaro (KAR) is a unique cultural tourism destination in Southwest Sumba Regency (SBD). This traditional village, which is located in the village of Maliti Bondo Ate, has traditional house buildings with quite unique shapes, historical tours in the form of stone graves, and Ratenggaro Beach natural attractions. This attraction makes many tourists come to visit the Ratenggaro Traditional Village. KAR tourism is now fully managed by indigenous peoples. This study aims to map the tourism communication model developed through the active involvement of indigenous peoples. This study is qualitative research using a case study approach. The study shows that the tourist destinations contained in the KAR highlighted the concept of tourism based on local branding by utilizing the local wisdom of the local community. Meanwhile, the involvement of local communities in KAR's tourism activities can be seen starting from tourism planning, and tourism promotion, to evaluation. The tourism communication model developed by KAR is based on indigenous peoples by placing the role of ndorumbaha (local tour guide) as a central figure in KAR tourism. Ndorumbaha is an essential figure in conducting KAR tourism communication. The ndorumbaha is tasked with conveying various information about what and how each KAR tourist attraction is to every visitor, both domestic and foreign. This tourism communication model in turn will be able to guarantee the creation of sustainable tourism with prominent local branding.

Child-led resistance in the streets of the global south: Decolonial perspectives of violence against children outside of family care

BackgroundViolence against children (VAC) remains an urgent global dilemma and researchers and policymakers alike continue to work tirelessly to devise strategies aiming to end VAC. However, the perspectives and expertise of children themselves remain underrepresented in the drafting and implementation of these strategies against VAC. This paper draws attention to the marginalization of children living outside of family care and centers their perspective. ObjectiveThis study aimed to characterize the forms of violence experienced by children living outside the family setting in Uganda, from the perspective of children themselves.The paper seeks to position the voicing of this perspective as a form of resistance against VAC from a decolonial perspective.Participants and Setting: The participatory research process included a total of 94 participants in various urban study sites in Kampala, Uganda. MethodsThe research team completed this qualitative study within a youth-driven participatory action research (YPAR) framework. Data collection techniques included interviews, focus groups, participatory visual methods and social cartography. ResultsChildren living outside of family care experience grave forms of emotional, physical and sexual violence. Child participants present survival strategies that can inform future research and policies on violence prevention practice. ConclusionsThe illustration of explicit violence outlined in this study represents a form of resistance children take against their perpetrators. The participatory youth researcher team urges future research and policy addressing VAC in Uganda to center these perspectives and expertise of children and adolescents in both programmatic and research initiatives aiming to end violence against children.

Założenia rowkowe o charakterze funeralnym ze stanowiska Domasław 10/11/12 / Chrzanów 4, pow. wrocławski jako przejaw oddziaływań kulturowych

The most interesting feature discovered in Domasław’s burial ground is the ditched enclosures complex of a funeral character. The oldest complex with a ring trench was dated to the middle Bronze Age (HaA2). This custom reaches its apogee in the early Iron Age (HaC). A total of 26 chamber graves encircled by trenches, as well as another ditch without a burial probably also from this period, were discovered in the cemetery. At the end of the Early Iron Age, burial practices within the Domasław necropolis did not cease completely. The category of sepulchral features with a younger chronology should also include the rectangular, nearly quadrangular structures which appear in the La Tene period and even at a later phase using this burial ground. The Domasław burials with surrounding trenches have no analogies in the nearest regions. Excavated circular structures make the largest group of funeral ditches to the north of the Carpathian and Sudeten Mountains. The influence on the shaping of the burial rite’s material remains as recorded in the form of chamber graves which stand out for their construction and furnishing, might be also treated as an element of impact. The appearance of circular ditches within this province might be also treated as an element of southern (Hallstatt) impact. The circular ditches at this burial ground is the manifestation of these influences. The strong impact from the Hallstatt circle probably led to profound changes in the sphere of beliefs, ideas, and social stratification. The custom of surrounding graves with rectangular ditches recorded in enclaves of the La Tène culture in Poland is undoubtedly the effect of the arrival of Celtic people from the south to these areas.

Inflammasome activation as a link between obesity and thyroid disorders: Implications for an integrated clinical management.

Obesity is strongly associated with chronic low-grade inflammation. Obese patients have an increased risk to develop thyroid autoimmunity and to became hypothyroid, suggesting a pathogenetic link between obesity, inflammation and autoimmunity. Moreover, type 2 diabetes and dyslipidemia, also characterized by low-grade inflammation, were recently associated with more aggressive forms of Graves’ ophthalmopathy. The association between obesity and autoimmune thyroid disorders may also go in the opposite direction, as treating autoimmune hyper and hypothyroidism can lead to weight gain. In addition, restoration of euthyroidism by L-T4 replacement therapy is more challenging in obese athyreotic patients, as it is difficult to maintain thyrotropin stimulation hormone (TSH) values within the normal range. Intriguingly, pro-inflammatory cytokines decrease in obese patients after bariatric surgery along with TSH levels. Moreover, the risk of thyroid cancer is increased in patients with thyroid autoimmune disorders, and is also related to the degree of obesity and inflammation. Molecular studies have shown a relationship between the low-grade inflammation of obesity and the activity of intracellular multiprotein complexes typical of immune cells (inflammasomes). We will now highlight some clinical implications of inflammasome activation in the relationship between obesity and thyroid disease.

Genocid nad Bošnjacima i demografske promjene na području Višegrada 1991-2013.

Commission of individual and mass crimes against values protected by international law, including the crime of genocide, was also directed towards changes in ethnic and demographic structures of population. All these are the features of fascistic, great state ideologies and policies. The most severe and most brutal forms of the implementation of the great state projects took place in the territory of the Republic of Bosnia and Herzegovina in 1992-1995. Namely, the great-Serbian genocidal ideology and policy has in continuity for more than two centuries practiced mass crimes against values protected by international law, including the crime of genocide against Bosniacs. Already in 1992, and independent, sovereign and internationally recognised Republic of Bosnia and Herzegovina was exposed to a brutal armed aggression by the neighbouring Federal Republic of Yugoslavia (Serbia and Montenegro). The objective of the aggression was fulfilment of several century long great state goal, and/or final completion of the space in which Serbs would dominantly live – the great Serbia. This goal was not possible without execution of grave forms of war crimes, namely in final destruction Bosnia and Herzegovina as a state and society. Impacts of such approach are particularly visible in the aspect of changes in demographic structure of population. Strategically important space for great-Serbian genocidal ideology and policy was and is the space of Bosnian Podrinje. Crime committed against Bosniacs in 1992-1995, including those committed in Višegrad, are essential part of the enforcement of the great-Serbian genocidal plan on making ethnically “clean” territories. According to 1991 census, there were 21,199 residents of Višegrad, of which 13,471 Bosniacs (63.54%) and 6,743 Serbs (31.80%). The Bosniacs of Višegrad were, especially in spring and summer of 1992, subjected to different forms of crimes, including mass murders, setting on fire, incarceration in camps, rapes, and persecution of civilians. Regardless of huge extent of crimes, the genocidal ideology was not given up even after the signing of the Dayton peace agreement. Adapted to peacetime conditions, even today, thirty years since the aggression, different forms of psychological and physical violence against Bosniacs have been used in Višegrad. Frequent attacks and harassment of returnees are followed by, for example line-up of members of the Ravna Gora Chetnic movement, a symbol of crimes against Bosniacs of Podrinje area in the WWII, or celebration of the Day of Russian Volunteers, who took part in the attacks and crimes against Podrinje Bosniacs during the aggression. Open discrimination and dehumanisation of Bosniacs returnees, permanent celebration of crimes and criminals are everyday events. All of this negatively affects continuation of the process of return of Bosniacs to their historic residence. The analysis of the contents of the relevant archives, especially two relevant censuses in Bosnia and Herzegovina (1991 and 2013) shall elaborate the demographic changes, which took place in Višegrad in this relevant period. It is the fact that the Bosniacs are today the absolute minority in Višegrad, which is the result of the committed crimes, including the genocide against Bosniacs, which ultimately resulted in the altered ethnic demographic structure of population. Višegrad is also subjected to a fast process of ageing, both due to the reduced number of returnees and due to the emigration of biologically productive population. Even all the other demographic indicators suggest that Višegrad is becoming the town of old people and general societal hopelessness, which shall be also detailed in the paper. This is also one of the ways to fully implement the practice of ethnically clean “Serb” territories. Nowadays, the political leaders of the smaller BiH entity and municipality Višegrad are preoccupied with the policy of denial of Bosniacs identity markers and provision of hopelessness for returnees, which finally brings no good to population in general, regardless of their ethnic background.

Selenium supplements: is it advisable to use them in treatment of pathology of the thyroid gland?

The article is a review of the literature in Scopus, Web of Science, MedLine and The Cochrane Library and is devoted to the analysis of the evidence base of the use of selenium supplements for the treatment of thyroid pathology. Despite the variety of thyroid pathology: changes in size and structure, hypo- and hyperfunction, autoimmune, oncopathology, there are not so many drugs used in its medical treatment. Drugs that are justified for various thyroid pathologies include iodine, levothyroxine and, to some extent, triiodothyronine, thyrostatics (methimazole, carbimazole, propylthiouracil), radioactive iodine and glucocorticoids, such as beta-blockers. Acute thyroiditis requires the appointment of antibacterial therapy, and oncopathology— specific chemotherapeutic agents, the effectiveness of which, unfortunately, is not high, and the frequency of appointment is significant. Along with these drugs, selenium drugs have become unprecedented in the last decade in thyroid pathology as a component of possible pathogenetic therapy. These drugs are prescribed to patients with diametrically opposed functional state of the thyroid gland, autoimmune pathology, nodules. It appears that thyroid carcinogenesis remains the only pathology where the use of selenium drugs is not recommended, although there are studies that indicate a link between thyroid cancer and selenium deficiency. The results of clinical studies and meta-analyzes are provided through the prism of a survey of Italian and European endocrinologists on the appointment of selenium drugs for the treatment of relevant thyroid pathology. The lack of evidence base for the use of selenium in most types of pathology of the thyroid gland: autoimmune thyroiditis, overt and subclinical hypothyroidism, Graves’ disease. According to most studies, the supplementation of selenium to therapy increases its plasma level, affects the activity of selenoproteins and level of antithyroid antibodies, but in no way affects the main clinical parameters such as thyroid hormones, levothyroxine dose, clinical symptoms. In general, the use of selenium in thyroid pathology cannot be considered appropriate, except for a mild form of Graves’ orbitopathy. Significant differences in the data of clinical trials and recommendations of thyroid societies with a real frequency of selenium administration by practitioner for the treatment and prevention of thyroid pathology are indicated.

Community practice and religion at an Early Islamic cemetery in highland Central Asia

Archaeological studies of Early Islamic communities in Central Asia have focused on lowland urban communities. Here, the authors report on recent geophysical survey and excavation of an Early Islamic cemetery at Tashbulak in south-eastern Uzbekistan. AMS dating places the establishment of the cemetery in the mid-eighth century AD, making it one of the earliest Islamic burial grounds documented in Central Asia. Burials at Tashbulak conform to Islamic prescriptions for grave form and body deposition. The consistency in ritual suggests the existence of a funerary community of practice, challenging narratives of Islamic conversion in peripheral areas as a process of slow diffusion and emphasising the importance of archaeological approaches for documenting the diversity of Early Islamic communities.

Accounting for Enhanced Interrogation: Elite Perspectives

ABSTRACT The Enhanced Interrogation programme was a medicalized initiative that used serious violence, at the least approaching torture in its severity, to extract information from detainees during the War on Terror. The programme’s activities are now widely viewed as grave forms of institutionally deviant behavior and have been condemned as such, including by health professional groups. While a considerable amount of research has been conducted into the Enhanced Interrogation programme there is currently a lack of research into elite perspectives on Enhanced Interrogation. This article analyses public accounts from lawyers, CIA Directors, and Government officials who were linked with the programme to examine how these individuals made sense of Enhanced Interrogation and how they sought to explain and assess it. The article maps the accounts of these individuals on to the justification framework developed by Scott and Lyman. The article highlights differences as well as similarities in the accounts of these elites.

Burial practices in early Byzantine Syro-Palestine (4th–7th centuries CE) – review article

The paper summarises current knowledge of burial customs in Syro-Palestine in the early Byzantine period (4th–7th centuries CE). It identifies elements that constituted the continuation of burial practices from the Roman period (1st–3rd centuries CE) as well as new customs. It includes the location of burial grounds, forms of graves, the variety of grave goods and body positioning. Quantitative research has demonstrated a gradual departure from chamber tombs and sarcophagi in the early Byzantine period. Burials in monasteries and, to a lesser extent, churches were a completely new trend that appeared during this period, related to the spread of Christianity. The paper also proposes a more widespread use of radiocarbon dating and stable isotope analysis. The results of such studies would deepen knowledge of burial customs in Syro-Palestine in the final phases of antiquity.

Role of MRCP to determine the etiological spectrum, level and degree of biliary obstruction in obstructive jaundice.

Obstructive jaundice as a result of hepatocellular disease many a times is indistinguishable from jaundice due to extrahepatic biliary obstruction based on just clinical and biochemical examinations. It is one of the most frequent and grave form of hepatobiliary disease which may lead to complications like ascending cholangitis, malabsorption and hepatorenal syndrome, thus demanding urgent surgical intervention. Thus not only early diagnosis but also accurate identification of level and cause of obstruction is crucial in managing these patients. The aim of this study is to evaluate the role of MRCP in the determination of the etiological spectrum, to evaluate level and degree of biliary obstruction in cases of obstructive jaundice, and to correlate MRCP findings with surgical/histopathology/ERCP findings where possible. It is an observational study done after the Institutional Ethics Committee (I.E.C.)- 2 approval. (IEC no: IEC/HMPCMCE/122/Faculty/8/186/20) Outdoor and indoor patients referred to radiodiagnosis department of Shree Krishna Hospital, Karamsad, for MRCP with clinical and laboratory parameters suggesting obstructive jaundice were included in the study. Patients less than 10 years of age, those with contraindications to MRI and patients with clinico-laboratory evidence of perihepatic/hepatic jaundice were excluded. A total of 50 patients were included after taking an informed consent from each patient. Demographic data, clinical details were recorded and collated along with MRI findings. Descriptive statistics was used to explore MRI findings and findings were correlated with surgical/histopathology/ERCP findings whichever applicable. The MRI scan was performed with 5 mm thick axial T1W, T2W and STIR, 5 mm thick coronal T1W, T2W and STIR TRUFIS, Thin coronal T2 FS, Thick coronal T2 FS, T2W coronal respiratory trigger sequences, 3-5 mm thick T2 weighted Haste and 3D sequence. Analysis was performed using STATA (14.2). Descriptive statistics was used of study population. Sensitivity and specificity value was used to compare the modality and individually calculated for various causative factors of jaundice. Of the 50 patients, 9 had CBD stones, it is observed that MRCP has sensitivity and specificity of 100% and 100%, respectively, in detecting Bile duct stones, whereas sensitivity and specificity of ERCP was 87.5% each. About 11 patients had CBD strictures, which were seen as narrowing of CBD with upstream dilatation. It was observed in our study that the sensitivity of MRCP was 93% and specificity was 95% in detecting CBD strictures while ERCP had 100% sensitivity and specificity. About 12 patients had CBD tumor for sensitivity and specificity of MRCP and ERCP was 100%. Out of 50 patients, 36% had gall bladder stones in whom MRCP sensitivity and specificity was 88.89% and 100% and was found to comparable with ERCP. Only three patients in our study had ampullary carcinoma out of which the sensitivity and specificity came 100% for MRCP. One patient, in whom MRCP and HPE detected ampullary carcinoma, ERCP detected no ampullary carcinoma thus favoring MRCP. However, owing to inadequate study population results are inconclusive. There is significant difference between MRCP and ERCP accuracy rate in detection of ampullary carcinoma. Therefore, our study which is more in favor of MRCP. There were 78% patients who were detected with biliary duct dilatation in ERCP, which was equally detected in MRCP. Thus MRCP had 100% sensitivity and specificity in detecting biliary duct dilatation compared to ERCP. Pancreatic dilatation was detected in four patients and there were two patients who were detected with ampullary stones and its sensitivity, specificity came up to 100% compared to ERCP. Conclusion: Thus to conclude, MRCP has high sensitivity for CBD such as stones, strictures and malignancies therefore to avoid unnecessary diagnostic ERCP; in cases with suspicion (clinical/CBD-IHBR dilatation on USG) of choledocholithiasis/ampullary stone, MRCP is recommended.

Role of Magnetic Resonance Cholangiopancreatography and Ultrasound as a Diagnostic Tool in Suspected Cases of Biliary Obstruction: A Prospective Cohort Study

Introduction: Obstructive jaundice is a common and grave form of hepatobiliary disease. It can pose problems in diagnosis and management, particularly intrahepatic cholestasis. Magnetic Resonance Cholangiopancreatography (MRCP) and Ultrasound (USG) are the frontline modality for biliary and pancreatic duct imaging. Aim: To evaluate the accuracy of USG and MRCP in assessing the level and cause of biliary obstruction which were compared with pathological or surgical findings. Materials and Methods: This prospective cohort study was conducted in the Department of Radiodiagnosis in a teriary care hospital from August 2013 to August 2015. Total 60 patients who were referred from the Department of Surgery and Medicine with strong clinical suspicion of biliary obstruction and altered Liver Function Test (LFT) were included in the study. All these patients underwent USG examination within a day of MRCP. Patients with previous biliary surgery and in whom Magnetic Resonance Imaging (MRI) was contraindicated were excluded. As a gold standard, the authors used ERCP, histological test and pathological findings after surgical intervention. The data collected was statistically analysed; sensitivity and specificity were calculated by using true and false positive and/or negative fractions. Results: The majority of patients were females and in sixth decade of life. The diagnostic accuracy of USG in detecting level of obstruction was comparable with MRCP. USG was 100% accurate in detecting hilar and suprapancreatic obstructions. In infrapancreatic obstructions diagnostic accuracy of USG was 95% as pancreatic head and peripancreatic region are poorly visualised on ultrasonography due to bowel gas shadows. Diagnostic accuracy of USG in the present study was 98.3%, one false negative case was of a small, soft, 4 mm calculus in distal Common Bile Duct (CBD). Sensitivity and specificity of USG in differentiating cystic from solid masses was 100%. Conclusion: The USG with improved technology and operator experience should be considered as the first choice in the diagnostic imaging of obstructive biliary disease. If the suspicion posed by clinical and laboratory findings are not confirmed at USG, the diagnosis must be achieved with the aid of MRCP.

PENGGALIAN POTENSI WISATA RELIGI DAN SEJARAH MAKAM PANJANG

The Long Tomb is located in Drajat Village, Kesambi District. The Drajat village area has several potential for pilgrimage tourism, namely in the form of graves and makom which contributed to the spread of Islam in Cirebon around the 15th century, especially in the spread of Islam in the Drajat village. In this article, we focus on the potential for long tombs to be used as potential for religious tourism. The purpose of this study is to describe religious tourism and the meaning of pilgrimage at the Long Tomb. The research method used is descriptive qualitative, by conducting in-depth interviews with the caretaker as the source of the long tomb. The Long Tomb is the resting place of a figure of Sultan Lelana who is known by the public as Prince Jaka Lelana. Jaka Lelana is the second son of Sunan Gunung Jati. The Long Tomb is sacred because Jaka Lelana is a descendant of the Guardian and is the son of Sunan Gunung Jati. Currently, the potential for long tomb pilgrimages is still very minimal and poorly maintained, so a strategy is needed to disseminate the potential to become one of the pilgrimage tourist destinations in Cirebon City.

Reticular Dysgenesis-Associated Adenylate Kinase 2 Deficiency Impairs Purine Metabolism and Ribosomal Biogenesis during Myelopoiesis

Reticular Dysgenesis (RD) is a particularly grave form of severe combined immunodeficiency (SCID), characterized by maturation arrest of both myeloid and lymphoid lineages paired with sensorineural hearing loss. RD is caused by biallelic mutations in the mitochondrial enzyme adenylate kinase 2 (AK2). AK2 catalyzes the phosphorylation of adenosine monophosphate (AMP) to adenosine diphosphate (ADP) in the mitochondrial intermembrane space. Using a CRISPR/Cas9 AK2 biallelic knock out model in human hematopoietic stem and progenitor cells (HSPCs), we have shown that AK2 -/- HSPCs mimic the neutrophil maturation defect in RD patients. Mitochondrial respiration is compromised in AK2 -/- HSPCs, which leads to a decreased NAD +/NADH ratio resulting in reductive stress. Metabolomics analysis by LC-MS/MS showed a significant accumulation of AMP, along with increased AMP/ADP and AMP/ATP ratios in AK2 -/- HSPCs, suggesting that purine metabolism is compromised by AK2 deficiency. Purine metabolism defects, such as deficiencies in adenosine deaminase (ADA) and purine nucleotide phosphorylase (PNP), have long been recognized as a cause of SCID. Furthermore, pharmacological interference with purine metabolism is a highly effective antiproliferative strategy in cancer therapy. In this study, we sought to investigate whether impaired purine metabolism contributes to the myelopoietic defect caused by AK2 deficiency.ResultsWe explored how purine metabolism affects myelopoiesis by differentiating HSPCs in media containing no nucleosides (nucleoside-), mixed nucleosides (nucleoside+) or adenosine only (adenosine+). We observed no difference in proliferation or neutrophil maturation between nucleosides- and nucleoside+ media for both control and AK2 -/- HSPCs, suggesting that AK2 -/- HSPCs do not rely on exogenous nucleosides. Interestingly, control HSPCs cultured in adenosine+ media showed severe proliferation and neutrophil maturation defects that mimic AK2 deficiency, suggesting that purine imbalance is detrimental to myelopoiesis.Previous metabolomics analysis showed a significant accumulation of inosine monophosphate (IMP) in AK2 -/- HSPCs. Since IMP can be produced through AMP deamination by AMPD, we asked whether the IMP accumulation in AK2 -/- HSPCs is caused by converting excess AMP to IMP. An LC-MS/MS analysis showed that AMPD inhibitor (AMPDi) treatment significantly lowered IMP levels and increased AMP levels in AK2 -/- HSPCs, indicating that AMP deamination is a major source of IMP accumulation in AK2 -/- HSPCs. Furthermore, AMPDi treatment did not improve, but rather slightly aggravated neutrophil differentiation in AK2 -/- HSPCs, suggesting that the AK2 -/- neutrophil maturation defect is not caused by IMP accumulation. This raises the possibility that AK2 -/- HSPCs employ AMP deamination as a mechanism to curtail the toxicity of excess AMP.Since purine is a building block of RNA, and ribosomal RNA (rRNA) constitutes >85% of cellular RNA content, we asked whether rRNA synthesis is compromised by AK2 deficiency. Pyronin Y staining showed a significant decrease in rRNA content in AK2 -/- HSPCs. Nascent peptide synthesis rate was also decreased in AK2 -/- HSPCs, as quantified by OP-puromycin uptake. These findings are corroborated by RNA-seq analysis of AK2 -/- and control HSPCs, which showed that ribosomal subunits, ribosomal biogenesis and ribonucleoprotein complex assembly are among the top down-regulated pathways. The data suggest that defective purine metabolism in AK2 -/- HSPCs impairs ribosomal biogenesis and protein synthesis.ConclusionOur studies showed that purine imbalance in HSPCs impairs myeloid proliferation and neutrophil maturation. AK2 depletion in HSPCs leads to AMP accumulation and defective ribosomal biogenesis. AK2 -/- HSPCs convert excess AMP to IMP, possibly as a means to mitigate AMP toxicity. However, AMP deamination activities alone are not sufficient to lower AMP levels to those of control HSPCs. We are currently testing whether boosting 5'-nucleotidase activities (cNIA, cN1B and cNII) in AK2 -/- HSPCs can decrease AMP levels and rescue the neutrophil maturation defect. As purine metabolic defects are associated with diverse immune and non-immune abnormalities, further understanding of how purine metabolism governs differentiation of human HSPCs will enable us to develop novel therapeutic strategies for RD and other purine disorders. DisclosuresPorteus: CRISPR Therapeutics: Current equity holder in publicly-traded company; Allogene Therapeutics: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Versant Ventures: Consultancy; Ziopharm: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Graphite Bio: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Morrison: Garuda Therapeutics: Other: founder and SAB member ; Kojin Therapeutics: Other: SAB member ; Frequency Therapeutics: Other: SAB member ; Ona Terapeutics: Other: SAB member ; Protein Fluidics: Other: SAB member .