The Role of Packaging Size on Contamination Rates during Simulated Presentation to a Sterile Field

Objective

The objective of this study was to assess the impact of package size on the contact between medical devices and non-sterile surfaces (i.e. the hands of the practitioner and the outside of the package) during aseptic presentation to a simulated sterile field. Rationale for this objective stems from the decades-long problem of hospital-acquired infections. This work approaches the problem from a unique perspective, namely packaging size.

Design

Randomized complete block design with subsampling.

Setting

Research study conducted at professional conferences for surgical technologists and nursing professionals.

Participants

Ninety-seven healthcare providers, primarily surgical technologists and nurses.

Methods

Participants were gloved and asked to present the contents of six pouches of three different sizes to a simulated sterile field. The exterior of pouches and gloves of participants were coated with a simulated contaminant prior to each opening trial. After presentation to the simulated sterile field, the presence of the contaminant on package contents was recorded as indicative of contact with non-sterile surfaces and analyzed in a binary fashion using a generalized linear mixed model.

Results

Recruited subjects were 26–64 years of age (81 females, 16 males), with 2.5–44 years of professional experience. Results indicated a significant main effect of pouch size on contact rate of package contents (P = 0.0108), whereby larger pouches induced greater rates of contact than smaller pouches (estimates±SEM: 14.7±2.9% vs. 6.0±1.7%, respectively).

Discussion and Conclusion

This study utilized novel methodologies which simulate contamination in aseptic presentation. Results of this work indicate that increased contamination rates are associated with larger pouches when compared to smaller pouches. The results add to a growing body of research which investigate packaging''s role in serving as a pathway for product contamination during aseptic presentation. Future work should investigate other packaging design factors (e.g. material, rigidity, and closure systems) and their role in contamination.     

Nucleotides part LXXX: Synthesis of 3'-O fluorescence labeled thymidine derivatives and their 5'-O-triphosphates

A new labeling technique attaching a fluorescent pteridine derivative (3, 5) via a linker onto the 3'-OH group of 5'-O-dimethoxytritylthymidine (7) was developed to lead to the conjugates 8 and 11. After detritylation to give 9 and 12, the final conversion into the corresponding 5'-triphosphates (13, 14), which were isolated as sodium salts, was performed by known methods.     

Kinase inhibitors modulate huntingtin cell localization and toxicity

Two serine residues within the first 17 amino acid residues of huntingtin (N17) are crucial for modulation of mutant huntingtin toxicity in cell and mouse genetic models of Huntington's disease. Here we show that the stress-dependent phosphorylation of huntingtin at Ser13 and Ser16 affects N17 conformation and targets full-length huntingtin to chromatin-dependent subregions of the nucleus, the mitotic spindle and cleavage furrow during cell division. Polyglutamine-expanded mutant huntingtin is hypophosphorylated in N17 in both homozygous and heterozygous cell contexts. By high-content screening in live cells, we identified kinase inhibitors that modulated N17 phosphorylation and hence huntingtin subcellular localization. N17 phosphorylation was reduced by casein kinase-2 inhibitors. Paradoxically, IKKβ kinase inhibition increased N17 phosphorylation, affecting huntingtin nuclear and subnuclear localization. These data indicate that huntingtin phosphorylation at Ser13 and Ser16 can be modulated by small-molecule drugs, which may have therapeutic potential in Huntington's disease.     

L-type calcium channel β subunit modulates angiotensin II responses in cardiomyocytes

Angiotensin II regulation of L-type calcium currents in cardiac muscle is controversial and the underlying signaling events are not completely understood. Moreover, the possible role of auxiliary subunit composition of the channels in Angiotensin II modulation of L-type calcium channels has not yet been explored. In this work we study the role of Ca(v)β subunits and the intracellular signaling responsible for L-type calcium current modulation by Angiotensin II. In cardiomyocytes, Angiotensin II exposure induces rapid inhibition of L-type current with a magnitude that is correlated with the rate of current inactivation. Semi-quantitative PCR of cardiomyocytes at different days of culture reveals changes in the Ca(v)β subunits expression pattern that are correlated with the rate of current inactivation and with Angiotensin II effect. Over-expression of individual b subunits in heterologous systems reveals that the magnitude of Angiotensin II inhibition is dependent on the Ca(v)β subunit isoform, with Ca(v)β(1b) containing channels being more strongly regulated. Ca(v)β(2a) containing channels were insensitive to modulation and this effect was partially due to the N-terminal palmitoylation sites of this subunit. Moreover, PLC or diacylglycerol lipase inhibition prevents the Angiotensin II effect on L-type calcium channels, while PKC inhibition with chelerythrine does not, suggesting a role of arachidonic acid in this process. Finally, we show that in intact cardiomyocytes the magnitude of calcium transients on spontaneous beating cells is modulated by Angiotensin II in a Ca(v)β subunit-dependent manner. These data demonstrate that Ca(v)β subunits alter the magnitude of inhibition of L-type current by Angiotensin II.     

Influence of early stress on social abilities and serotonergic functions across generations in mice

Exposure to adverse environments during early development is a known risk factor for several psychiatric conditions including antisocial behavior and personality disorders. Here, we induced social anxiety and altered social recognition memory in adult mice using unpredictable maternal separation and maternal stress during early postnatal life. We show that these social defects are not only pronounced in the animals directly subjected to stress, but are also transmitted to their offspring across two generations. The defects are associated with impaired serotonergic signaling, in particular, reduced 5HT1A receptor expression in the dorsal raphe nucleus, and increased serotonin level in a dorsal raphe projection area. These findings underscore the susceptibility of social behaviors and serotonergic pathways to early stress, and the persistence of their perturbation across generations.