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As a part of our ongoing discovery efforts exploring azasugar as agents for treating various unmet medical needs, we prepared analogs of azasugar as potential anti-hepatitis C virus (HCV) agents. Herein we describe the synthesis of novel 2'β-C-Me 9-deazanucleoside azasugar analogs.

To study the safety of percutaneous vs open tracheostomy approaches on patients requiring long term ventilation in ICU setting. It is a prospective study done over a period of 2 years on 105 patients requiring long term ventilation in ICU set up in a tertiary care hospital. Patients were subjected to either open approach or percutaneous tracheostomy bedside in ICU itself. Then patients were followed during their hospital stay to look for any tracheostomy related complications. Data regarding age, gender, indications of long term ventilation and complications were compiled and analysis was done. It was found that most of the patients were of male gender (88.6%) in the age group of 50–59 years of age. The most common cause for tracheostomy was head injury secondary to road traffic accident, seen in 79 out of 105 cases. On comparing complications rate, there was no statistically significant difference in both the groups. However rate of peristomal infection is more with open approach group (P

Across the developing world, countries are experiencing rapid growth in urbanization and motorization. While high motorization rates potentially meant hat more people will be able to claim the benefits of improved accessibility to goods and services as a consequence of enhanced mobility, there are questions about the sustainability of this future. Will countries be able to build and maintain infrastructure to accommodate increasing numbers of vehicles? Will the increasing number of vehicles and their characteristics support attainment of the Sustainable Development Goals (SDGs) Will they put in jeopardy countries’ ability to meet their climate commitments under their Nationally Determined Contributions (NDCs)? From a development impact standpoint, the nature of a country’s motor vehicle stock and how it grows affects three key and tangible outcomes. First, the quality of the motor vehicle stock affects road safety outcomes—that is, the number of people killed or seriously injured in motor vehicle crashes. The characteristics of vehicles and their fitness or roadworthiness can affect fatality and serious injury outcomes. Second, the quality of the motor vehicle fleet affects air quality, particularly in cities. Motor vehicles are a key source of harmful air pollution, including carbon monoxide (CO), fine particulates (PM2.5), sulfur oxides (SOx), and ozone precursors (oxides of nitrogen and various hydrocarbons), and the amount of these pollutants they emit is directly related to how the vehicle was built and how well it is maintained. Finally, the profile of the vehicle fleet—what is the size and weight of vehicles in the fleet, how big are their engines, what kind of power control technology do they use, and how did their manufacturers engineer the technology of the vehicle to balance power with efficiency—affects the (fossil) fuel consumption of the vehicle stock as a whole, and, consequently, the greenhouse gas (GHG) emissions profile of the road transport sector. This report presents the World Bank’s Motorization Management (MM) framework, which is intended to support client countries in the development of policies and measures aimed at managing vehicle stocks in a proactive, phased, and systematic manner to make them safer, cleaner, and more fuel efficient. The MM framework reflects a series of policy considerations and programs that can be implemented to improve the quality of fuels and vehicles in a country’s stock.

Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that affects an estimated 1 in 50,000 individuals worldwide. Berotralstat (BCX7353) is the only small molecule approved by the US Food and Drug Administration (FDA) for the prophylactic treatment of HAE attacks in patients 12 years and older. During the discovery of BCX7353, we also identified a novel series of small molecules containing a quaternary carbon as potent and orally bioavailable Plasma Kallikrein (PKal) inhibitors. Lead compound was identified as a potent inhibitor following a detailed lead optimization process that balanced the lipophilic efficiency (LipE) and pharmacokinetic (PK) profile.

Background In patients with acute biliary pancreatitis (ABP), cholecystectomy is mandatory to prevent further biliary events, but the precise timing of cholecystectomy for mild to moderate disease remain a subject of ongoing debate. The aim of this study is to assess the outcomes of early versus delayed cholecystectomy. We hypothesize that early cholecystectomy as compared to delayed cholecystectomy reduces recurrent biliary events without a higher peri-operative complication rate. Methods Patients with mild to moderate ABP were prospectively randomized to either an early cholecystectomy versus a delayed cholecystectomy group. Recurrent biliary events, peri-operative complications, conversion rate, length of surgery and total hospital length of stay between the two groups were evaluated. Results A total of 72 patients were enrolled at a single public hospital. Of them, 38 were randomized to the early group and 34 patients to the delayed group. There were no differences regarding peri-operative complications (7.78% vs 11.76%; p = 0.700), conversion rate to open surgery (10.53% vs 11.76%; p = 1.000) and duration of surgery performed (80 vs 85 minutes, p = 0.752). Nevertheless, a greater rate of recurrent biliary events was found in the delayed group (44.12% vs 0%; p ≤ 0.0001) and the hospital length of stay was longer in the delayed group (9 vs 8 days, p = 0.002). Conclusion In mild to moderate ABP, early laparoscopic cholecystectomy reduces the risk of recurrent biliary events without an increase in operative difficulty or perioperative morbidity.

Motorization management is the process of shaping, through public policies and programs, the profile, quality, and quantity of the motor vehicle fleet as motorization occurs. Across Africa, governments are struggling to manage the effects of rapid motorization and urbanization. In the past two decades, Africa has been the fastest urbanizing region in the world, growing at 3.44 percent on average which is much higher than the rate of other rapid developing regions, such as Asia and Latin America. While this motorization potentially means that more African people will be able to claim the benefits of improved access to opportunities and mobility, it raises alarming questions about the sustainability of this future. Will countries be able to build and maintain infrastructure to accommodate these vehicles Will the quality of the vehicles support African development goals and the region’s ability to meet the sustainable development goals and climate obligations This report lays out plausible motorization policies that can be implemented by the government of Kenya.

Motorization management is the process of shaping, through public policies and programs, the profile, quality, and quantity of the motor vehicle fleet as motorization occurs. Across Africa, governments are struggling to manage the effects of rapid motorization and urbanization. In the past two decades, Africa has been the fastest urbanizing region in the world, growing at 3.44 percent on average which is much higher than the rate of other rapid developing regions, such as Asia and Latin America. Given that Africa remains the least developed region, the rapid urban growth pace will likely accelerate motorization development and challenge the limited resource base to meet the demand of the growing urban populations. While this motorization potentially means that more African people will be able to claim the benefits of improved access to opportunities and mobility, it raises alarming questions about the sustainability of this future. Will countries be able to build and maintain infrastructure to accommodate these vehicles Will the quality of the vehicles support African development goals and the region’s ability to meet the Sustainable Development Goals and climate obligations This report lays out plausible motorization policies that can be implemented by the government of Ethiopia.

Mullerian duct aplasia, Renal aplasia and Cervicothoracic Somite dysplasia (MURCS association) is a developmental field defect, diagnosed if both aplasia/hypoplasia of the Mullerian duct, renal agenesis/ectopy and anomalies of the cervicothoracic somites are present. We report a case of MURCS Association with the above features, absent hand, T12 Hemi vertebra and an exophytic bony outgrowth from C5 vertebra. An exophytic bony projection from the spinous process of C5 vertebra, presenting as a swelling over the neck has not been described previously as a skeletal malformation in MURCS Association. Absent hand as a skeletal malformation in MURCS association was not seen in the earlier literature. This case is reported since it adds to the wide spectrum of anomalies associated with MURCS association and helps in distinguishing MURCS association from the syndromes which may show overlap.

The report presents a rare case of carcinoid tumor in a 17 year female who presented with epigastric pain of one week duration. She was diagnosed to have type I choledochal cyst on abdominal ultrasound and MRI. She underwent total excision of choledochal cyst with roux-en-Y hepaticojejunostomy. Histopathological examination revealed a neuroendocrine tumor within choledochal cyst which was immunoreactive for Chromogranin A. Patient is well at 6 months of follow up. These tumors are characteristically slow-growing, therefore awareness of its presence preoperatively can facilitate optimal management by performing surgical resection with negative margins which offers the best chance of long-term survival.

An asymptomatic 47-year-old woman presented with an incidental pancreatic lesion. She had a history of hypertension and chronic renal impairment from ureteric calculi. Contrast-enhanced CT was done to assess the calculi after treatment (Fig. 1). It revealed a large complex cyst measuring 13.0 6.0 cm arising from the pancreatic body and tail. The cyst was septated, had solid components, and had a thick wall with calcifications. The serum amylase level was mildly elevated at 556 U/L (normal 0-220 U/L). Results of liver function tests and carbohydrate antigen 19-9 were normal. EUS showed a 5-cm cyst in the pancreatic body (Fig. 2). It had a thick wall and a solid component that appeared to arise from the wall. A Doppler signal was absent. The pancreatic duct was normal and did not communicate with the cyst. The biliary tree, left kidney, and left lobe of the liver and surrounding vessels also were normal, but the left adrenal gland could not be visualized. The cyst was provisionally diagnosed as a mucinous cystic neoplasm with potential malignant transformation. Central pancreatectomy was planned. At surgery, a well defined mass was found arising from the left adrenal gland, whereas the pancreas was normal. Left adrenalectomy was performed. During the operation, the patient’s blood pressure was labile, with transient increases requiring labetalol for control. Macroscopically, the mass was well defined and encapsulated. It had a 3-cm central cystic space containing brownish soft material. Histologically, it was composed of diffuse sheets of tumor cells arranged in zellballen and trabecular patterns (Fig. 3). The tumor cells had abundant basophilic to amphophilic cytoplasm (Fig. 4). They stained positive for chromogranin, synaptophysin, and neuronspecific enolase. The sustentacular framework stained positive for S-100 protein. These findings confirmed that the mass was a cystic PCC.

Thirty cases of the Landry-Guillain-Barre-Strohl syndrome (LGBS) seen at a medical center are reviewed. Three patients had autopsy-proved pulmonary embolism and seven additional patients fulfilled systematic clinical diagnostic criteria. The incidence of pulmonary embolism in the total group was probably in excess of 33 percent. Pulmonary embolism should be recognized as a frequent complication of LGBS and the effectiveness of prophylactic anticoagulation in this group should be evaluated.

A unique case of flame burns of the respiratory tract occurred during oxygen therapy. In this patient, prior to the onset of respiratory complications, there appeared to be a classical latent period requiring constant observation and attention. The tracheotomy was advantageous in removing the excessive secretions and necrotic tissue, and also facilitated the attachment of a ventilator. Large doses of steroids were definitely beneficial in relieving the severe bronchospasm. The importance of controlled volume ventilation is manifest.

Two hundred and eighty seven matched cultures of ventilator humidifying systems and the patient interface tubing taken at random over a three year period were evaluated. Bacteriologic contamination of tubing and humidifying svstems occurred as independent and separate events, although the incidence of contamination of tubing was significantly higher. Copper mesh air filtering placed in the humidification assembly had the lowest rate of contamination while ultrasonic humidifiers had the highest. The distribution of the bacteriologic population was unusual. Further improvement of "accepted techniques" to monitor and avoid bacteriologic equipment contamination are necessary.