New Oral Anticoagulants versus Warfarin for Cerebral Venous Thrombosis: A Multi-Center, Observational Study / 대한뇌졸중학회지

No abstract available.

overview of the most common enzyme defect, glucose-6-phosphate-dehydrogenase deficiency

Background: Glucose-6-Phosphate-Dehydrogenase [G6PD] deficiency is the most common enzyme deficiency globally and is more remarkable in certain parts of the world which had high malaria prevalence in the past. It is an X-linked genetically inherited disorder, where the first presentation can be neonatal jaundice. There are over 300 variants of this disorder based upon the genetics. Although the morbidity and mortality is not very high, the deficiency can be more appropriately managed by proper preventive methods which include screening and avoidance of trigger. Also prompt management of acute hemolysis can save a child from many complications

Methodology: we conducted this review using a comprehensive search of MEDLINE, PubMed, and EMBASE from January 1987 to March 2017. The following search terms were used: G6PD deficiency, prevalence of G6PD, genetics of G6PD deficiency, management and diagnosis of G6PD

Aim of the work: this study aimed to understand about the etiology, pathophysiology and study various lines of prevention and management of G6PD deficiency in pediatric age group

Conclusion: proper preventive and treatment methods can avoid negative effects on the child's quality of life and reduce morbidity and mortality, therefore the child's care takers must be well informed

use of intra-operative nerve monitoring [IONM] in thyroid surgery to reduce recurrent laryngeal nerve injury

Objectives: To assess the relation between use of Intraoperative nerve monitoring [IONM] in thyroid surgery and the prevalence of RLN injury, and to assess its significance of IONM in reduction of RLN injury among patients who underwent thyroid surgery

Background: Recurrent laryngeal nerve [RLN] palsy is one of the big concerns for surgeons during thyroid surgery. Surgeons tried to find ways to identify this nerve and preserve it. The most popularly used way is the use of Intraoperative nerve monitoring [IONM]

Methods: In this retrospective study, we collected the data for all cases that underwent thyroid surgery in Security Forces Hospital [SFH], Riyadh, Saudi Arabia during the period of 2010 to 2012. We divided participants to two groups, those who used IONM and those who did not used IONM. The statistical Package for Social Sciences [SPSS, version 22] was utilized for data entry and analysis. Categorical variables were described by frequencies and percentages. Descriptive analysis involving Chi-square test was used to test significance of association between categorical variables. The level of significance was set at P< 0.05

Results: Post-operation RLN injury was higher in those who underwent thyroid surgery without IONM, but the difference was insignificant [p=0.460]. Three of those patients who underwent the surgery without IONM has RLN injury [3.1%], and no RLN injury reported of those who underwent surgery with IONM [0%]

Conclusion: IONM could help in identifying the RLN and preserving it from injury. Although, in this study there were insignificant correlations between RLN injury and IONM. Further researches on a larger-scales is recommended to get more informative results and allow better comparison

Studies on antihyperlipidemic and endothelium modulatory activities of polyherbal formulation [POL[4]] and its ingredients in high fat dietfed rats

A compound herbal formulation [POL[4]] is used traditionally in interior parts [Distt. Badin] of Sindh, Pakistan, for the treatment of metabolic disorders like diabetes and hyperlipidemia. This study is aimed to determine the effectiveness of POL[4] and its ingredients in hyperlipidemia and associated endothelial dysfunction and hypertension. POL[4] is composed of equal proportion of Nigella sativa, Cichorium intybus, Trigonella foenum graecum and Gymnema sylvestre mixed in powdered form. Chronic [6 to 7 weeks] administration of POL[4] and its ingredients mixed in diet caused a notable attenuation in total cholesterol, low density lipoprotein cholesterol, triglycerides, atherogenic index, Creactive protein and glucose, while it has increased high density lipoprotein levels. POL[4] intervention markedly [p<0.01] reduced systolic blood pressure in rats to 127+/-1.92 vs. 145.4+/-1.07 mm of Hg using tail-cuff method and significantly [p<0.05] improved endothelium-dependent relaxation [75+/-2.88 vs. 82.75+/-1.22%] to acetylcholine in isolated aortae of rats in treatment groups using force transducer and PowerLab system. Similar activities were assessed on the part of ingredients of POL[4]. These findings indicate that POL[4] and its ingredients possess antihyperlipidemic, endotheliumdependent modulatory and antihypertensive activities, thus providing an evidence to the vernacular use of POL[4] in hyperlipidemia and hypertension

Silent peptic ulcer disease perforation

Objective: To determine the frequency of asymptomatic [silent] peptic ulcer disease [PUD] perforation and risk factors associated with it

Study design: Descriptive case series

Place and Duration of study: Surgical Unit 1, Ward-3 Jinnah Postgraduate Medical Centre [JPMC] Karachi, from January 2014 to December 2016

Methodology: All patients above twelve year of age operated due to peptic ulcer perforation with history of known case of PUD and asymptomatic patients with spontaneous perforation were included. Risk factors like H-pylori infection, use of NSAIDs, smoking, alcohol consumption, betel nut consumption and socioeconomic status were noted. Frequencies of asymptomatic and symptomatic PUD patients with perforations were determined and risk factors for both the groups were analyzed

Results: Total of 198 patients of acute peritonitis due to peptic ulcer perforation were operated in three year period. Among these 171 [86.34%] patients were male and 27 [13.64%] female. One hundred and fifty three [77.27%] patients had no previous history of PUD and 45 [22.73%] were known cases of PUD and partially treated. H-pylori was detected in 35/45 [77.77%] in symptomatic group and 115/153 [75.16%] in asymptomatic group. Smokers were 9/45[20%] in symptomatic group and 54/153 [35.29%] in asymptomatic group. NSAID and steroid users were 9/45 [20%] in symptomatic and 54/153 [35.29%] in asymptomatic group. Alcoholics were 18/45 [40%] in symptomatic and 27/153 [17.64%] in asymptomatic group. Betel nut was rare risk factor. All patients belonged to low socioeconomic group

Conclusions: Frequency of silent perforation was 77.27%. Major risk factors were H-pylori infection and NSAID use. Screening for H-pylori and use of antiulcer drugs can decrease the perforation of PUD

Quantification and further refinements of dorsal metacarpal artery perforator flap for reconstruction of wounds of fingers up to distal interphalangeal joints

Objective: to assess the outcome of dorsal metacarpal artery perforator flap for coverage of finger defects extending up to distal interphalangeal joint [DIPJ]

Study Design: case series

Place and Duration of Study: Jinnah Burn and Reconstructive Surgery Centre, Lahore, from March 2015 to May 2017

Methodology: our study was carried out in two parts. 1st part of study was to measure average flap length in our population. Five hundred cases were enrolled to measure flap length, from pivot point of the flap to the distal border of extensor retinaculum. This length was traced to fingers to determine its coverage area. This was followed by clinical study in 35 cases. All patients with wounds over dorsal surface of fingers up to distal interphalangeal joint and volar surface of fingers up to mid of middle phalanx, single or multiple finger defects with exposed tendon joints or bones were included in the study. Patients with history of trauma to the dorsum of hand, metacarpal head or neck fracture and patients with history of diabetes or peripheral vascular disease were excluded

Results: flap length decreased from radial to ulnar side of hand. Average length of flap based on the second metacarpal artery was 7cm while of the third was 6.6 cm and the fourth was 6.1 cm. This flap length covered up to mid of middle phalanx in border digits while up to PIPJ in central digits. This data was confirmed in 35 patients in whom 36 flaps were raised to cover finger defects. Thirty-four flaps survived completely while tip necrosis was seen in 2 cases

Conclusion: the dorsal metacarpal artery perforator flap is a thin, pliable flap, which has minimal donor-site morbidity. It can reliably cover soft tissue defects of dorsum of fingers up to mid of middle phalanx in border digits and up to PIPJ in central digits

Retrograde intrarenal surgery and percutaneous nephrolithotomy for the treatment of renal stones greater than 2 cm

Background: Stone size is a key factor in the determination of the success of treatment modalities. Recently, there has been a great advancement in technology for minimally invasive management of urinary stones such as percutaneous nephrolithotomy, ureteroscopy, shockwave lithotripsy, and retrograde internal Surgery

Aim of the Study: to assess and compare the efficacy of retrograde intrarenal surgery [RIRS] in the treatment of kidney stones greater than 2 cm versus percutaneous nephrolithotomy [PCNL]

Patients and methods: A retrospective analysis was carried out for a total of 118 patients, of which 46 patients underwent RIRS while 72 patients underwent PCNL between May 2013 and May 2017

Results: The mean duration of operation was 96.39 +/- 41.11 min in the RIRS group and 69.51 +/- 19.3 min in the PCNL group [p<0.001]. Hospital stay was significantly shorter in the RIRS group [1.32 +/- 0.6 vs. 4.19 +/- 1.9 days] in the RIRS and PCNL groups respectively [p<0.001]. Stone-free rates after one session were 67.4% and 90.3% of the RIRS and PCNL groups, respectively. Blood transfusions were required in two patients in the PCNL group. Complication rates were generally higher in the PCNL group

Conclusion: The present study concluded that RIRS can be a successful substitute to PCNL in the treatment of kidney stones with a diameter of 2-4 cm particularly in patients with comorbidities

Helicobacter pylori outer membrane protein Q genotypes and their susceptibility to anti-adhesive phytotherapeutic agents / 中西医结合学报

<p><b>OBJECTIVE</b>Helicobacter pylori is a Gram-negative organism. Its outer membrane protein Q (HopQ) mediates host-pathogen interactions; HopQ genotypes 1 and 2 are found associating with gastroduodenal pathologies. The authors measured the anti-adhesion effects of the extracts of Abelmoschus esculentus, Zingiber officinale, Trachyspermum ammi, Glycyrrhiza glabra, Curcuma longa and Capsicum annum against HopQ genotypes and H. pylori cytotoxin-associated gene A (CagA).</p><p><b>METHODS</b>DNA was extracted by polymerase chain reaction of the HopQ genotypes (i.e., type 1, type 2 and CagA) from 115 H. pylori strains. The effect of the extracts from selected dietary ingredients was determined using a gastric adenocarcinoma cell line and a quantitative DNA fragmentation assay. The anti-adhesive effect of these extracts on H. pylori was tested using an anti-adhesion analysis.</p><p><b>RESULTS</b>C. annum, C. longa and A. esculentus showed prominent anti-adhesion effects with resultant values of 17.3% ± 2.9%, 14.6% ± 3.7%, 13.8% ± 3.6%, respectively, against HopQ type 1 and 13.1% ± 1.7%, 12.1% ± 2%, 11.1% ± 1.6%, respectively, against HopQ type 2. C. longa (93%), C. annum (89%) and A. esculentus (75%) had better anti-adhesive activity against H. pylori with HopQ type 1 compared to HopQ type 2 with respective values of 70%, 64% and 51%. Extracts of C. annum (14.7% ± 4.1%), A. esculentus (12.3% ± 4.1%) and Z. officinale (8.4% ± 2.8%) had an anti-adhesion effect against CagA-positive H. pylori strains compared to CagA-negative strains.</p><p><b>CONCLUSION</b>The anti-adhesion properties of the tested phytotherapeutic dietary ingredients were varied with HopQ genotypes. HopQ type 1 was found to be more sensitive to extracts of C. annum, C. longa and A. esculentus compared to the HopQ type 2 genotype.</p>

Modifiable determinants of attitude towards dengue vaccination among healthy inhabitants of Aceh, Indonesia: Findings from a community-based survey

Objective To explore and understand the attitude towards dengue vaccination and its modifiable determinants among inhabitants of Aceh (northern Sumatra Island, Indonesia), the region that was most severely affected by the earthquake and tsunami of 26 December 2004. Methods A community-based, cross-sectional study was conducted among 535 healthy inhabitants in nine regencies (Kabupaten or Kotamadya) of Aceh that were selected randomly from November 2014 to March 2015. A set of validated, pre-tested, structured questionnaires was used to guide the interviews. The questionnaires covered a range of explanatory variables and one outcome variable (attitude to dengue vaccination). Multi-step logistic regression analysis and Spearman's rank correlation were used to test the role of explanatory variables for the outcome variable. Results More than 70% of the participants had a poor attitude towards dengue vaccination. Modifiable determinants associated with poor attitude to dengue vaccination were low education level, working as farmers and traditional market traders, low socioeconomic status and poor knowledge, attitude and practice regarding dengue fever (P < 0.05). The KAP domain scores were correlated strongly with attitude to dengue vaccination, rs = 0.25, rs = 0.67 and rs = 0.20, respectively (P < 0.001). Multivariate analysis found that independent predictors associated with attitude towards dengue vaccination among study participants were only sex and attitude towards dengue fever (P < 0.001). Conclusions This study reveals that low KAP regarding dengue fever, low education level and low socioeconomic status are associated with a poor attitude towards dengue vaccination. Therefore, inhabitants of suburbs who are working as farmers or traditional market traders with low socioeconomic status are the most appropriate target group for a dengue vaccine introduction program.

Antiacanthamoebic properties of natural and marketed honey in Pakistan

Objective To determine antiacanthamoebic activity of natural and marketed honey samples. Methods Natural honey samples were collected directly from the bee hive and marketed honey samples were purchased from the local market in Karachi, Pakistan. Both honey samples were tested for their flavonoid content (quercetin equivalent per gram of the extract) and phenolic content (gallic acid equivalent per gram). Furthermore, their antioxidant activity was determined by measuring 2,2-diphenyl-1-picrylhydrazyl. Using amoebistatic and amoebicidal assays, the effects of honey samples were tested against growth and viability of Acanthamoeba parasites. Results Natural honey exhibited potent amoebistatic and amoebicidal effects, in a concentration-dependent manner. Honey-treated Acanthamoeba castellanii showed loss of acanthopodia, following which amoebae detached, rounded up, reduced in size, decreased in cytoplasmic mass and they were observed floating in the culture medium. Importantly, honey-treated amoebae did not revive when inoculated in fresh growth medium, however, glycerol-treated amoebae exhibited viable trophozoite and active growth. In contrast, marketed honey samples varied in their efficacy against Acanthamoeba castellanii. The proportion of flavonoid, as determined by quercetin measurements and the proportion of phenolic, as determined by gallic acid measurements was higher in natural honey compared with marketed honey. Similarly, the antioxidant activity, as determined by 2,2-diphenyl-1-picrylhydrazyl scavenging activity was higher in natural honey vs. marketed honey. Conclusions This study shows that natural honey has antiacanthamoebic properties and possesses higher flavonoid, phenolic and antioxidant properties compared with the marketed honey. These findings are of concern to the public, health officials, and to the manufacturers regarding production of honey for medical applications.

Measurement of platelet function to determine the prevalence of aspirin non?responsiveness among Saudi type II diabetic patients

Introduction: Aspirin is widely used as either a primary or secondary preventive measure in of cardiovascular events however, platelets from diabetic patients are less responsive to aspirin and are unable to protect themselves from thrombotic events

Objective and Method: 180 diabetic patients were enrolled for measuring their platelet aggregation. The aim was to evaluate the prevalence of aspirin non?responsiveness among Saudi type II diabetic patients. Serum glucose level and other clinical data were collected to find out the possible determinant of reduced platelet sensitivity to aspirin

Results: The prevalence of aspirin non?responsiveness was 9.44%. A significant correlation between aspirin test and each of fasting blood sugar, HbA1c, cholesterol and platelet count was observed. In contrast, there was no correlation among aspirin non?response, body mass index, age or hypertension

Conclusion: The relationship between the levels of glucose in the blood and aspirin resistance relates the importance of controlling blood glucose in diabetic patients to guarantee better aspirin action. Regular examining of type II diabetic patients to determine the sensitivity of platelet to the antiplatelet therapy is necessary to protect them from the risks of cardiovascular complications

Frequency of early atrial fibrillation in post mitral valve replacement surgery

Objective: To determine the frequency of atrial fibrillation after mitral valve replacement surgery

Methodology: This study was performed in cardiac surgery ward of Lady reading Hospital [LRH] Peshawar. It was a descriptive cross sectional study. Data was collected from 1.3.2014 to 28.02.2015. Statistical analyses were performed using SPPS version 14. Mean +/- SD were used for quantitative and Frequencies and percentages were used for categorical variables

Results: Total 120 patients undergone through mitral valve replacement. Male patients were 48 [40%], Mean age of the study population was 46.20 years +/- 9.14SD. Atrial fibrillation [AF] was observed in 45 [37.5%] patients. Post operative AF was similar between both gender and all ages

Conclusion: Atrial fibrillation is common finding in patients undergoing Mitral valve replacement surgery and is not affected by age and sex

Frequency of acute kidney injury in patients undergoing coronory artery bypass grafting

Objective: To find the frequency of acute kidney injury in patients undergoing coronary artery bypass grafting

Methodology: The study was conducted in cardiovascular unit Lady Read-ing Hospital Peshawar. It was cross sectional study. Sampling technique was non probability convenient sampling. Data was collected from 20.2.2013 to 20.8.2013. Total 179 patients included in the study. All patients with known coronary artery disease were included in the study whom were planned for revascularization in the form of coronary artery bypass grafting [CABG]. Post-operatively all patients' serum creatinine till 48th post op hour was observed to detect acute kidney injury. Acute Kidney Injury [AKI] was defined as more than 50% or elevation of 0.3 mg/dl of creatinine level from base line

Results: A total of 179 patients undergoing coronary artery bypass grafting were included in the study. Average age of the patients was 46.88 years +/- 9.91 with range 20-60 years. Patients were divided into four groups according to age. The acute kidney injury after coronary artery bypass grafting was observed in 14 [7.82%] patients. Acute kidney injury was more common in old age and it was non significantly more common in male gender

Conclusion: In spite of current highly advance cardiac surgery techniques and post operative care still there is high incidence of acute kidney injury following revascularization and subsequent worst outcomes

Modifiable determinants of attitude towards dengue vaccination among healthy inhabitants of Aceh, Indonesia: Findings from a community-based survey

OBJECTIVE@#To explore and understand the attitude towards dengue vaccination and its modifiable determinants among inhabitants of Aceh (northern Sumatra Island, Indonesia), the region that was most severely affected by the earthquake and tsunami of 26 December 2004.@*METHODS@#A community-based, cross-sectional study was conducted among 535 healthy inhabitants in nine regencies (Kabupaten or Kotamadya) of Aceh that were selected randomly from November 2014 to March 2015. A set of validated, pre-tested, structured questionnaires was used to guide the interviews. The questionnaires covered a range of explanatory variables and one outcome variable (attitude to dengue vaccination). Multi-step logistic regression analysis and Spearman's rank correlation were used to test the role of explanatory variables for the outcome variable.@*RESULTS@#More than 70% of the participants had a poor attitude towards dengue vaccination. Modifiable determinants associated with poor attitude to dengue vaccination were low education level, working as farmers and traditional market traders, low socioeconomic status and poor knowledge, attitude and practice regarding dengue fever (P < 0.05). The KAP domain scores were correlated strongly with attitude to dengue vaccination, rs = 0.25, rs = 0.67 and rs = 0.20, respectively (P < 0.001). Multivariate analysis found that independent predictors associated with attitude towards dengue vaccination among study participants were only sex and attitude towards dengue fever (P < 0.001).@*CONCLUSIONS@#This study reveals that low KAP regarding dengue fever, low education level and low socioeconomic status are associated with a poor attitude towards dengue vaccination. Therefore, inhabitants of suburbs who are working as farmers or traditional market traders with low socioeconomic status are the most appropriate target group for a dengue vaccine introduction program.

Bipolar electrofulguration with endoscopic approach in allergic hypertrophied turbinate

Background: Allergic hypertrophied turbinate, is managed by different treatment modalities, with variable outcome

Objective: To evaluate the result of bipolar electrofulguration with endoscopic approach in allergic hypertrophied turbinate

Patients and Methods: Study design: Descriptive, cross sectional study. Place: ENT department of Jaber AL - Ahmed Forces Hospital, Kuwait from 1[st] January 2008 to 31[st] December 2010. Fifty five cases of hypertrophy of Inferior turbinate were selected. Forty patients were females and 15 were males. They presented mainly with history of nasal blockage. Endoscopic bipolar diathermy was used to decrease the size of inferior turbinate. The variables included were nasal obstruction, post nasal drip, itching and sneezing. The patient were followed up on one, three and 6 month. The data was entered and analyzed by SPSS version 12

Results: Endoscopic bipolar diathermy showed good results after follow upto two six months duration. We found that 89% of the patients reported subjective improvement and 65% of the patients have objective improvement as well

Conclusion: Bipolar diathermy of inferior turbinate using zero degree endoscope is a good technique for excellent view of inferior turbinate. This procedure gives good results to the patients

Regurgitated presentation of extranasopharyngeal angiofibroma in emergency

OBJECTIVE: To add more knowledge about extra-nasopharyngeal angiofibroma presentation

STUDY DESIGN: Case Report

SETTING: ENT Department of Jaber AL Ahmed Armed Forces Hospital, Kuwait

PATIENT AND METHODS: An old man of 65 years presented in emergency department with regurgitated angiofibroma of right vallecular region. It was excised from its site of origin with no complications

RESULTS: Excision was complete and follow up showed no recurrence

CONCLUSION: Extra-nasopharyngeal angiofibroma is a very rare entity. Complete excision will result in no complication and recurrence

Frequency of complete heart block after surgical closure of perimembranous ventricular septal defect

Objective: to find the frequency of complete heart block [CHB] in patients undergoing surgical perimembranous Ventricular septal defect [VSD] closure

Methodology: this was a Descriptive cross sectional study performed in Cardiovascular Department Lady Reading Hospital Peshawar. Data was collected from 28 January 2013 to 28 July 2013 with sample size of 103.Sampling technique was non probability consecutive. All patients with perimembranous ventricular septal defect, aged 5 years to 25 years with any gender were included in the study

Results:-mean age was 12.63 years +/- 6.63. Patients were divided in four categories according to their age. Over all complete heart block in the perimembranous ventricular septal defect after surgical closure was 10[9.71%]. Age wise distribution of complete heart block shows that majority of the complete heart block 6[12.8%] were found in age less than or equal to 10 years

Conclusion:-VSD closure is less often associated with CHB but there should be arrangements for pace maker to timely pace the patient in case of any emergency

Hypoglycaemic effects of methanolic extract of Canscora decussata [Schult] whole-plant in normal and alloxan-induced diabetic rabbits

In present study hypoglycaemic effects of the crude powdered C. decussata and its methanolic extract [ME] in alloxan diabetic rabbits were evaluated. The hypoglycaemic effect was measured by blood glucose, insulin level, HbA1c and his to pathology of pancreas. Glucose lowering effect of the ME was studied in diabetic rabbits. The effects of extract on blood glucose, body weight, food in take, fluid intake, OGTT were also evaluated. The results showed that 0.5,1 and 2g/kg of the powder significantly decreased blood glucose levels in normal rabbits and diabetic rabbits at the intervals checked. Oral intake of pioglitazone also reduced the levels in these rabbits. Synergistic hypoglycaemic effect of 600mg/kg of ME with different doses of insulin [2 and 3unit/kg, s/c] further reduced blood glucose levels of treated alloxan-diabetic rabbits. The oral glucose tolerance test revealed lowered area under curve values in ME treated rabbits. Treatment with ME [400 and 600 mg/kg] for 30 days showed highly significant decrease in blood glucose level by augmenting insulin secretion, HbA1cand significant increase in body weight, serum insulin levels in treated diabetic rabbits. Histopathology study showed regeneration of beta -cells. These studies have, therefore, supported the traditional use of this herb in diabetic patients

early experience of laproscopic cholecystectomy from K.M.C / civil hospital Khairpur Mir's

Objective: To see feasibility, per operative difficulties and overall results of lap: Cholecystectomy in our newly established minimal invasive surgical setup

Study Design: Randomized Descriptive study

Place and Duration of Study: This study was conducted in Surgical Department of newly established Khairpur Medical College/ Civil Hospital Khairpur Mir's from August 2014 to May 2015

Materials and Methods: The data of all the 100 patients with the diagnosis of gall stone disease was entered in specific proforma, who were admitted at K.M.C / Civil Hospital Khairpur Mir's. The consent for laproscopic procedure was taken prior to surgery. All the base line blood and radiological investigations were done. Cardiac and general anesthesia opinion were also taken. The procedure was carried out by conventional "four port" method on scheduled elective operation list

Results: In this study male to female ratio was 1:6.1 and mean age was 38.5 years. In 52 patients gall bladder was non inflamed and callot's triangle was clear but in 48 cases various kinds of abnormalities were present. In 40% cases operative technique was modified by different means. Conversion rate remained 09%. In 56 cases operative time was 40 mints, in remaining 44 patients it was beyond 40 mints. Post operatively 26 patients developed various minor and major complications. There was no mortality in our series

Conclusion: Lap: Cholecystectomy is safe and effective procedure, applicable to any general as well as teaching hospital. Over all our results are acceptable according to the national and international studies