An efficient access to β-ketosulfones via β-sulfonylvinylamines: metal–organic framework catalysis for the direct C–S coupling of sodium sulfinates with oxime acetates

A copper-based framework Cu₂(OBA)₂(BPY) was synthesized and used as a recyclable heterogeneous catalyst for the synthesis of β-sulfonylvinylamines from sodium sulfinates and oxime acetates via direct C–S coupling reaction. The transformation was remarkably affected by the solvent, and chlorobenzene emerged as the best option. This Cu-MOF displayed higher activity than numerous conventional homogeneous and MOF-based catalysts. The catalyst was reutilized many times in the synthesis of β-sulfonylvinylamines without considerably deteriorating in catalytic efficiency. These β-sulfonylvinylamines were readily converted to the corresponding β-ketosulfones via a hydrolysis step with aqueous HCl solution. To the best of our knowledge, this direct C–S coupling reaction to achieve β-sulfonylvinylamines was not previously conducted with a heterogeneous catalyst.

Cu₂(OBA)₂(BPY) was used as catalyst for the synthesis of β-sulfonylvinylamines from sodium sulfinates and oxime acetates. These β-sulfonylvinylamines were readily converted to corresponding β-ketosulfones via a hydrolysis step.     

Thyrotropin-secreting pituitary adenoma presenting as hypokalemic periodic paralysis

Thyrotropin (TSH)-secreting pituitary adenoma presenting with hypokalemic periodic paralysis is extraordinarily rare and may be misdiagnosed. We describe a 44-year-old man who suffered from acute muscle weakness and inability to ambulate upon awakening in the morning. Physical examination showed hypertension, tachycardia, and symmetrical flaccid paralysis of all extremities. The major biochemical abnormality was hypokalemia (K+, 2.0 mmol/L) with low urine K+ excretion. A thyroid function study revealed elevated thyroid hormone levels and inappropriately high TSH concentrations (2.10 microU/mL). Brain magnetic resonance imaging delineated a pituitary tumor with suprasellar extension. After trans-sphenoidal removal of tumor, he became clinically and biochemically euthyroid without any further attack of paralysis. Pathological findings confirmed a TSH-secreting adenoma with exclusive TSH immunostaining. TSH-secreting pituitary adenoma must be kept in the differential diagnosis in any thyrotoxic periodic paralysis patients with detectable TSH levels to avoid delaying diagnosis and management.     

Factors for prolonged length of stay after elective hepatectomy for hepatocellular carcinoma. The surgeon's role in the managed care era

BACKGROUND/AIMS: Length of stay is an important marker of medical resource consumption. In the modern managed care era physicians are driven to deliver the highest quality of care while using fewest resources. Hepatectomy represents a technically challenging and resource-intensive procedure, particularly in the setting of hepatic malignancy and liver cirrhosis. For improving quality of surgical management in such cases, we aimed to identify the factors affecting length of stay after hepatectomy for patients with hepatocellular carcinoma. METHODOLOGY: A total of 375 consecutive surgical hepatocellular carcinoma patients at a tertiary referral center during a 7-year period were reviewed. Length of stay after hepatectomy longer than 14 days was defined as prolonged length of stay. Patients were divided into two groups according to their length of stay. Patients with length of stay less than or equal to 14 days were in Group A and those with length of stay longer than 14 days were in Group B. Data for comparative analysis between both groups were categorized according to preoperative patients' clinical demographic factors, operation-related factors, and pathological factors. The significant univariate factors were used for subsequent multivariate analysis. RESULTS: The significant independent factors were patients' preoperative prothrombin activity, intraoperative blood transfusion, surgical complication, and the time to abdominal drain removal. Among these independent factors, surgical complication (p < 0.001, relative risk 7.01, and 95% confidence interval 3.46 to 14.18) was the most powerful factor for prolonged length of stay after elective hepatectomy for hepatocellular carcinoma. CONCLUSIONS: Most of the independent factors for prolonged length of stay after elective hepatectomy for hepatocellular carcinoma patients are operation-related and surgeon-dependent. The surgeon plays a key role in determining length of stay. By minimizing blood transfusion, surgical complication, and the time to abdominal drain removal, length of stay can be significantly decreased in hepatocellular carcinoma patients undergoing hepatectomy.     

S6K1 controls pancreatic β cell size independently of intrauterine growth restriction

Type 2 diabetes mellitus (T2DM) is a worldwide heath problem that is characterized by insulin resistance and the eventual loss of β cell function. As recent studies have shown that loss of ribosomal protein (RP) S6 kinase 1 (S6K1) increases systemic insulin sensitivity, S6K1 inhibitors are being pursued as potential agents for improving insulin resistance. Here we found that S6K1 deficiency in mice also leads to decreased β cell growth, intrauterine growth restriction (IUGR), and impaired placental development. IUGR is a common complication of human pregnancy that limits the supply of oxygen and nutrients to the developing fetus, leading to diminished embryonic β cell growth and the onset of T2DM later in life. However, restoration of placental development and the rescue of IUGR by tetraploid embryo complementation did not restore β cell size or insulin levels in S6K1^–/– embryos, suggesting that loss of S6K1 leads to an intrinsic β cell lesion. Consistent with this hypothesis, reexpression of S6K1 in β cells of S6K1^–/– mice restored embryonic β cell size, insulin levels, glucose tolerance, and RPS6 phosphorylation, without rescuing IUGR. Together, these data suggest that a nutrient-mediated reduction in intrinsic β cell S6K1 signaling, rather than IUGR, during fetal development may underlie reduced β cell growth and eventual development of T2DM later in life.     

Rankings versus reality in pancreatic cancer surgery: a real-world comparison

Background

Patients are increasingly confronted with systems for rating hospitals. However, the correlations between publicized ratings and actual outcomes after pancreatectomy are unknown.

Methods

The Massachusetts Division of Health Care Finance and Policy Hospital Inpatient Discharge Database was queried to identify pancreatic cancer resections carried out during 2005–2009. Hospitals performing fewer than 10 pancreatic resections in the 5-year period were excluded. Primary outcomes included mortality, complications, median length of stay (LoS) and a composite outcomes score (COS) combining primary outcomes. Ranks were determined and compared for: (i) volume, and (ii) ratings identified from consumer-directed hospital ratings including the US News & World Report (USN), Consumer Reports, Healthgrades and Hospital Compare. An inter-rater reliability analysis was performed and correlation coefficients (r) between outcomes and ratings, and between rating systems were calculated.

Results

Eleven hospitals in which a total of 804 pancreatectomies were conducted were identified. Surgical volume correlated with overall outcome, but was not the strongest indicator. The highest correlation referred to that between USN rank and overall outcome. Mortality was most strongly correlated with Healthgrades ratings (r = 0.50); however, Healthgrades ratings demonstrated poorer correlations with all other outcomes. Consumer Reports ratings showed inverse correlations.

Conclusions

The plethora of publicly available hospital ratings systems demonstrates heterogeneity. Volume remains a good but imperfect indicator of surgical outcomes. Further systematic investigation into which measures predict quality outcomes in pancreatic cancer surgery will benefit both patients and providers.     

Planning and implementation of community oral health programs for caries management in children

Tooth decay or cavities (dental caries) can have a significant impact on children's quality of life, causing pain, infection, and other problems in the oral environment. Good oral health is a fundamental element of good general health for children, yet dental caries is still prevalent among children in many countries. Dental caries is well-understood, and effective prevention is an attainable goal. Dental professionals should actively engage with communities--in particular, the underprivileged--to identify dental caries problems and implement appropriate and effective community oral health programs (COHPs) to improve oral health and reduce oral health inequalities. This paper discusses COHPs as well as the steps involved in caries prevention for children. These steps cannot ensure the success of every COHP, but they are helpful for developing, integrating, expanding, and enhancing them. The effectiveness of COHPs for the prevention of caries in children varies from country to country, according to cultural, social, economic, and health care settings. Careful consideration of the local situation is required when selecting the elements of COHPs.     

Cloning and expression in E. coli of a functional Fab fragment obtained from single human lymphocyte against anthrax toxin

Human lymphocytes derived from the blood of a donor immunized with anthrax vaccine were isolated and enriched for B-cells by Nycoprep density centrifugation. Individual anti-anthrax protective antigen (PA) B-cells were isolated by fluorescence activated cell sorting with fluorescence-labeled recombinant PA (rPA). The RNA from sorted single B-cells was extracted using plant total RNA as the carrier prior to purification by Nanoprep RNA isolation columns and then cDNA was prepared. Donor specific human Fab primer sets were developed based on rapid amplification of 5'-complementary DNA end results. Heavy chain and light chain of human Fab were amplified from the donor single B-cells by PCR. The amplified heavy and light chain were then cloned into the expression vector pASK-IBA2 and expressed in Escherichia coli (E. coli). The chains combined in vivo to form a functional Fab which was then purified as one protein. The human Fab antibodies produced by this technique were functional when tested in Western blots where the rPA was the target as well as in ELISA. This approach allowed us to obtain human Fab that retained the natural heavy and light chain pairing, which is supposed to have a high antigen-binding affinity.