Activated natural killer cells and interleukin-2 promote granulocytic and megakaryocytic reconstitution after syngeneic bone marrow transplantation in mice

Purified populations of natural killer (NK) cells were obtained from mice with severe combined immune deficiency (SCID). SCID spleen cells were cultured and activated with recombinant human interleukin-2 (rhIL- 2) in vitro. The activated NK cells were then transferred with syngeneic BALB/c bone marrow cells (BMC) and rhIL-2 into lethally irradiated syngeneic recipients to determine their effect on long-term hematopoietic reconstitution. On analysis, the transfer of rhIL-2- activated NK cells along with BMC resulted in significant increases in splenic and BM hematopoietic progenitor cells when compared with those for mice not receiving NK cells. Histologic and flow cytometric analysis showed a marked increase in granulocytic and megakaryocytic lineage cells present in the spleens of the mice receiving activated NK cells. Analysis of the peripheral blood indicated that the transfer of activated NK cells with BMC also significantly improved platelet and total white blood cell counts, with increases in segmented neutrophils. Erythroid recovery was not affected. Finally, lethally irradiated mice receiving activated NK cells and rhIL-2 along with limiting numbers of syngeneic BMC showed a marked increase in survival rate. These results show that the use of populations enriched for activated NK cells after syngeneic BM transplantation (BMT) has a profound enhancing effect on engraftment primarily affecting megakaryocytic and granulocytic cell reconstitution. Therefore, the transfer of activated NK cells and rhIL- 2 may be of clinical use to promote hematopoietic reconstitution after BMT.     

Reduced Effectiveness of Interruptive Drug-Drug Interaction Alerts after Conversion to a Commercial Electronic Health Record

Background

Drug-drug interaction (DDI) alerts in electronic health records (EHRs) can help prevent adverse drug events, but such alerts are frequently overridden, raising concerns about their clinical usefulness and contribution to alert fatigue.

Objective

To study the effect of conversion to a commercial EHR on DDI alert and acceptance rates.

Design

Two before-and-after studies.

Participants

3277 clinicians who received a DDI alert in the outpatient setting.

Intervention

Introduction of a new, commercial EHR and subsequent adjustment of DDI alerting criteria.

Main Measures

Alert burden and proportion of alerts accepted.

Key Results

Overall interruptive DDI alert burden increased by a factor of 6 from the legacy EHR to the commercial EHR. The acceptance rate for the most severe alerts fell from 100 to 8.4%, and from 29.3 to 7.5% for medium severity alerts (P?<?0.001). After disabling the least severe alerts, total DDI alert burden fell by 50.5%, and acceptance of Tier 1 alerts rose from 9.1 to 12.7% (P?<?0.01).

Conclusions

Changing from a highly tailored DDI alerting system to a more general one as part of an EHR conversion decreased acceptance of DDI alerts and increased alert burden on users. The decrease in acceptance rates cannot be fully explained by differences in the clinical knowledge base, nor can it be fully explained by alert fatigue associated with increased alert burden. Instead, workflow factors probably predominate, including timing of alerts in the prescribing process, lack of differentiation of more and less severe alerts, and features of how users interact with alerts.

     

Perianal anatomy in non-abused preschool children

The purpose of this study was to describe the normal variation in perianal anatomy in preschool children, selected for non-abuse, and to compare the findings in two examination positions. A letter of invitation was sent to 3773 children, after which 305 children (103 boys and 202 girls) were recruited. Inclusion in the study was based on self-selection, whereby parents who did not suspect any occurrence of sexual abuse of their child gave informed consent to participate. The mean age of the children was 5.63 y (range: 5.13-6.75). An anal examination was performed in the left lateral position (LLP) and the prone knee-chest position (KCP), for approximately 30 s each. A colposcope and a camera were used. All data were systematically analysed for gender differences, and a paired sample test was used to compare findings in LLP and KCP. Venous congestion in LLP and external anal dilatation in both positions were significantly more common in girls, while midline depressions and smooth areas (both positions) were significantly more common in boys. External and total anal dilatation, midline smooth areas and depressions and the occurrence of a prominent anal verge were significantly more common in the KCP. The finding of total anal dilatation was rare. CONCLUSION: We observed several gender and position differences in perianal anatomy, and most of these findings seem to be related to structure and tone in the anal muscles.     

ENDOMETRIOMA OF THE LIVER

Hepatic endometriosis is extremely rare. The diagnosis is often missed and treatment is delayed. A 37-year-old woman was referred to the gynaecology department with vague abdominal pains. She had a past history of pelvic endometriosis and hysterectomy with bilateral salpingo-oophorectomy. Further investigations in due course confirmed it to be endometriosis of the liver. She was eventually referred to the hepatobiliary unit, almost three years after her first presentation, where she was operated on with good results.     

Increased number of substitutions in the D-loop of mitochondrial DNA in the sudden infant death syndrome

The purpose of the present study was to investigate substitutions in the D-loop of mitochondrial DNA (mtDNA) in sudden infant death syndrome (SIDS) and controls, since several observations indicate the involvement of mtDNA mutations in SIDS. These include elevated levels of vitreous humour hypoxanthine in SIDS victims, familial clustering without mendelian traits, and observations of increased sleepiness and a lower activity score in infants who later succumbed to SIDS. Eighty-two cases of SIDS and 133 controls were investigated and the D-loop sequences were recorded in the base-pair range 16 055-16 500 in the mtDNA sequence. The sequencing was carried out using the Applied Biosystems Sequenase dye terminator method and a ABD373A sequencer. The recorded D-loop sequences were compared with the Cambridge sequence and differences were recorded as substitutions. The SIDS cases had a tendency towards a higher substitution rate in the D-loop than the controls ( p = 0.088). This observation makes it interesting to search for deleterious mutations in other locations in the mtDNA.     

High Performance Thin Layer Chromatography Fingerprint Profile of Rhizome Extracts of Five Important Curcuma Species

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - The genus Curcuma (Family: Zingiberaceae) has 80 different species. Some of the species have been used...     

Interfacial Adhesion of Thick NiTi Coating on Substrate Stainless Steel

Interfacial adhesion of thick NiTi coating on substrate stainless steel is investigated here. NiTi coating was deposited on the substrate by using the thermal plasma spraying method. Deposition of NiTi coating was carried out by using various levels of input power under an Ar atmosphere. Multiple coating layers were deposited on the stainless steel surface for a specific thickness. The cross-section of the plasma-sprayed samples were prepared and characterized by using various techniques. The hardness of the coating layers on the surface and cross-section was examined. The thickness of the coating increased with the increase in power. No cracks were detected in the interface for the NiTi coating deposited at 12 kW power. However minor pores were observed at some regions along the interface at the sample prepared at 9 kW power. A good-quality coating layer was formed at the interface of the substrate. Primary phases of austenite and martensite were confirmed from the EBSD and XRD investigations. There was the presence of intermetallic and oxide phases in the coating layers. A less heat-affected zone of 10 µm of along the interface was confirmed without any diffusion of elements from the substrate to the coating layers. There was homogenous distribution elemental composition of Ni and Ti throughout the coating layers.     

Evaluation of scleral incisions and their effects on corneal curvature in manual small-incision cataract surgery

Purpose:Incisions in cataract surgery can be modified in various ways in terms of size, shape, and axis to reduce or tailor astigmatism. This study was conducted to examine the effect of site (superior vs, temporal) and shape (frown vs. V-shaped, chevron) of scleral incisions for cataract surgery on corneal curvature.Methods:The prospective study was carried out on 200 consecutive patients with senile cataract and who were planned for surgery at a tertiary eye hospital in north India. The placement of the incision was decided by the steeper corneal meridian—whether superior or temporal—and then patients of these two groups were randomized for frown and V-shaped incision; in this way, four groups of 50 patients each were formed. Follow-up was done on day 1, at 2 weeks, 4 weeks, 8 weeks, and 12 weeks. At each follow-up, post-operative keratometry with routine postoperative examination was done. The results were statistically analyzed by using student’s t-test, Chi-squared test, and the Pearson correlation coefficient.Results:In all the four groups, the difference of preoperative astigmatism and surgically-induced astigmatism was statistically highly significant. The analysis of uncorrected visual acuity (UCVA) was statistically significant (P < 0.05) on postoperative day 1 and at 2, 4, and 12 postoperative weeks; it was statistically insignificant (P > 0.05) at postoperative week 8.Conclusion:Temporal incisions result in lesser postoperative surgically induced astigmatism (SIA) than superior incisions. Chevron incisions result in minimal change in corneal curvature. This effect can be utilized to tailor the postoperative astigmatism.