High yielding synthesis of 2,2'-bipyridine macrocycles, versatile intermediates in the synthesis of rotaxanes.

We present an operationally simple approach to 2,2'-bipyridine macrocycles. Our method uses simple starting materials to produce these previously hard to access rotaxane precursors in remarkable yields (typically >65%) across a range of scales (0.1-5 mmol). All of the macrocycles reported are efficiently converted (>90%) to rotaxanes under AT-CuAAC conditions. With the requisite macrocycles finally available in sufficient quantities, we further demonstrate their long term utility through the first gram-scale synthesis of an AT-CuAAC [2]rotaxane and extend this powerful methodology to produce novel Sauvage-type molecular shuttles.

Correction: High yielding synthesis of 2,2'-bipyridine macrocycles, versatile intermediates in the synthesis of rotaxanes.

[This corrects the article DOI: 10.1039/C6SC00011H.].

Somatic cell nuclear transfer in the sheep induces placental defects that likely precede fetal demise.

The efficiency of cloning by somatic cell nuclear transfer (SCNT) is poor in livestock with approximately 5% of transferred cloned embryos developing to term. SCNT is associated with gross placental structural abnormalities. We aimed to identify defects in placental histology and gene expression in failing ovine cloned pregnancies to better understand why so many clones generated by SCNT die in utero. Placentomes from SCNT pregnancies (n = 9) and age matched, naturally mated controls (n = 20) were collected at two gestational age ranges (105-134 days and 135-154 days; term = 147 days). There was no effect of cloning on total placental weight. However, cloning reduced the number of placentomes at both gestational ages (105-134 days: control 55.0 +/- 4.2, clone 44.7 +/- 8.0 and 135-154 days: control 72.2 +/- 5.1, clone 36.6 +/- 5.1; P < 0.001) and increased the mean individual placentome weight (105-134 days: control 10.6 +/- 1.3 g, clone 18.6 +/- 2.8 g and 135-154 days: control 6.6 +/- 0.6 g, clone 7.0 +/- 2.0 g; P < 0.02). Placentomes from cloned pregnancies had a significant volume of shed trophoblast and fetal villous hemorrhage, absent in controls, at both gestational age ranges (P < 0.001) that was shown to be apoptotic by activated caspase-3 immunoreactivity. Consequently, the volume of intact trophoblast was reduced and the arithmetic mean barrier thickness of trophoblast through which exchange occurs was altered (P < 0.001) at both gestational age ranges in clones. In addition, cloning reduced placental expression of key genes in placental differentiation and function. Thus, cloning by SCNT results in both gross and microscopic placental abnormalities. We speculate that trophoblast apoptosis, shedding, and hemorrhage may be causal in fetal death in ovine clones.

Finding relief from TEFRA cost limits.

The Tax Equity and Fiscal Responsibility Act (TEFRA) limits cost-per-case rate increases for inpatient care delivered by healthcare providers excluded from Medicare's prospective payment system. Costs beyond these limits normally are not reimbursed. Under certain circumstances, however, healthcare providers can receive reimbursement beyond TEFRA limits by petitioning for an adjustment from their fiscal intermediaries and the Health Care Financing Administration. Although the request process often is lengthy, providers who can thoroughly document substantial increases in the cost of delivering care due to extraordinary circumstances, significant wage, increases, or noncompatibility of cost-reporting periods may be granted relief in the form of a rate adjustment and, in rare cases, the assignment of a new base year.

Are multiple examinations of the gall-bladder helpful?

The pattern of use of the oral cholecystogram and ultrasonocholecystography in the investigation of 1014 patients prior to cholecystectomy was analysed. Three hundred and sixty-eight (36.3%) of our patients had both an oral cholecystogram and an ultrasound examination of the gallbladder. In 193 (52.4%) of these the initial investigation was positive: the second test in this group was rarely helpful and sometimes confusing. Overall the predictive value of a positive first study was 98.5%. We conclude that the use of further investigation following an initially positive result is not justified. By these criteria 18.5% of patients had an unnecessary second investigation.