ABO maternal-child discordance: Evidence of variable allelic expression and considerations for investigation.

BACKGROUND: We report a case of apparent mother-child ABO group noninheritance. A Caucasian mother initially typed as group O and her infant group AB. Investigation ruled out preanalytical causes such as mislabeled samples and in vitro fertilization. MATERIALS AND METHODS: Red blood cells were characterized by routine serologic testing. Genomic data were analyzed by targeted polymerase chain reaction-restriction fragment length polymorphism and Sanger sequencing. Transferase structures were modeled using PyMOL molecular visualization software. RESULTS: Serologic testing initially demonstrated the mother was group O, father group AB, and infant group AB. Further testing of the maternal sample with anti-A,B demonstrated weak A expression. Molecular testing revealed the maternal sample had an ABO*O.01.01 allele in trans to an A allele, ABO*AW.29 (c.311T>A, p.Ile104Asn), determined by gene sequencing. The sample from the infant carried the same ABO*AW.29 allele in trans to a B allele, ABO*B.01. CONCLUSION: ABO genotyping revealed an A transferase encoded by ABO*AW.29, with apparent variable activity. Although A antigen expression is well known to be weak in newborns, it was robust on the red blood cells (RBCs) of the AB infant and undetectable with anti-A on the mother. Variable expression of weak subgroups may reflect competition or enhancement by a codominant allele, as well as glycan chain maturation on red cells. Previous examples in group AB mothers with Aweak infants suggested that the decreased expression is primarily due to glycan immaturity. To our knowledge, this is the first reported case of the ABO*AW.29 allele presenting with weak A expression in a group Aweak mother and robust A expression in a group AB infant, suggesting the in trans allele is an important factor in determining transferase activity and may override age-related effects.

Enhancement in MS-based peptide detection by microfluidic free-flow zone electrophoresis.

Matrix components are known to significantly alter the ionization of a target analyte in ESI-based measurements particularly when working with complex biological samples. This issue however may be alleviated by extracting the analyte of interest from the original sample into a relatively simple matrix compatible with ESI mass-spectrometric analysis. In this article, we report a microfluidic device that enables such extraction of small peptide molecules into an ESI-compatible solvent stream significantly improving both the sensitivity and reproducibility of the measurements. The reported device realizes this analyte extraction capability based on the free-flow zone electrophoretic fractionation process using a set of internal electrodes placed across the width of the analysis channel. Employing lateral electric fields and separation distances of 75 V/cm and 600 µm, respectively, efficient extraction of the model peptide human angiotensin II was demonstrated allowing a reduction in its detection limit by one to three orders of magnitude using the ESI-MS method. The noted result was obtained in our experiments both for a relatively simple specimen comprising DNA strands and angiotensin II as well as for human serum samples spiked with the same model peptide.

Measurement of ambient gamma dose rate in Metro Manila, Philippines, using a portable NaI(TI) scintillation survey meter.

Radiological data such as ambient dose equivalent rate obtained from radiation monitoring in Metro Manila are useful for the detection of any anomalous increase of radiation dose rate levels due to nuclear or radiological emergencies. In this study, ambient dose equivalent rates were measured in different locations in Metro Manila using a portable NaI(Tl) scintillation survey meter to determine the background radiation levels within the capital. Ambient dose equivalent rates measured range from 32.7 ± 2.2 to 59.3 ± 8.7 nanosieverts per hour (nSv/h) with computed mean and median values of 41.7 and 39.6 nSv/h, respectively. These values were lower than the Philippines' average dose rate which is 52 nanograys per hour (nGy/h). No significant trend was also observed in the monthly variation of ambient dose equivalent rate for most locations, with the dose rates being relatively consistent throughout a year. No significant trend was further observed in the monthly variation of ambient dose equivalent rate for the whole Metro Manila. Data obtained in this study were used to develop a dose rate distribution map of Metro Manila which could be used as a baseline reference of emergency responders for environmental radioactivity monitoring during nuclear or radiological emergencies that may affect Metro Manila.

The Current Burden of Follow-up of Stage 1A1 Cervical Cancer.

OBJECTIVE: The aim of this study was to assess the current burden and consistency of stage 1A1 cervical cancer follow-up within Greater Glasgow and Clyde Health Board. METHODS: A retrospective review was undertaken of women diagnosed with and treated of, between 2007 and 2011, stage 1A1 cervical cancer in Greater Glasgow and Clyde Health Board. Data were collected on referral cytology, definitive method of treatment, posttreatment cytology, and rate of recurrence. Outcomes included rate of recurrence, abnormal cytology, and number of interventions during follow-up. RESULTS: Of the 78 women diagnosed with stage 1A1 cervical cancer, 43 had a LLETZ (large loop excision of the transformation zone) as definitive treatment. Ninety percent of stage 1A1 cervical cancers were diagnosed following abnormal screening cytology. Almost 86% of all cytology post-LLETZ were negative. Only 1 woman had a recurrence. No posthysterectomy vault smears were low-grade dyskaryosis or worse. CONCLUSIONS: There is a very low rate of abnormal cytology after LLETZ. Vault smears are of limited benefit in the management of women posthysterectomy for stage 1A1 cervical cancer.

Electrophoretic extraction of low molecular weight cationic analytes from sodium dodecyl sulfate containing sample matrices for their direct electrospray ionization mass spectrometry.

While the use of sodium dodecyl sulfate (SDS) in separation buffers allows efficient analysis of complex mixtures, its presence in the sample matrix is known to severely interfere with the mass-spectrometric characterization of analyte molecules. In this article, we report a microfluidic device that addresses this analytical challenge by enabling inline electrospray ionization mass spectrometry (ESI-MS) of low molecular weight cationic samples prepared in SDS containing matrices. The functionality of this device relies on the continuous extraction of analyte molecules into an SDS-free solvent stream based on the free-flow zone electrophoresis (FFZE) technique prior to their ESI-MS analysis. The reported extraction was accomplished in our current work in a glass channel with microelectrodes fabricated along its sidewalls to realize the desired electric field. Our experiments show that a key challenge to successfully operating such a device is to suppress the electroosmotically driven fluid circulations generated in its extraction channel that otherwise tend to vigorously mix the liquid streams flowing through this duct. A new coating medium, N-(2-triethoxysilylpropyl) formamide, recently demonstrated by our laboratory to nearly eliminate electroosmotic flow in glass microchannels was employed to address this issue. Applying this surface modifier, we were able to efficiently extract two different peptides, human angiotensin I and MRFA, individually from an SDS containing matrix using the FFZE method and detect them at concentrations down to 3.7 and 6.3 µg/mL, respectively, in samples containing as much as 10 mM SDS. Notice that in addition to greatly reducing the amount of SDS entering the MS instrument, the reported approach allows rapid solvent exchange for facilitating efficient analyte ionization desired in ESI-MS analysis.

A microfluidic SPLITT device for fractionating low-molecular weight samples.

In this article, we report the design of a microfluidic split flow thin cell (SPLITT) fractionation device with internal electrodes placed across the width of its analysis channel for assaying low-molecular weight samples. The reported device allows the realization of lateral electric fields and separation distances of the orders of 100 V/cm and 500 µm, respectively, that are suitable for fractionating such mixtures with high resolution. Our experiments show that a key challenge to realizing electrophoretic fractionations using the current design is to minimize the electroosmotically driven fluid circulations in its SPLITT channel that tend to hydrodynamically mix the liquid streams flowing through this duct. The present work addresses this challenge by chemically modifying the surface of our fluidic conduits with a new coating medium, N-(2-triethoxysilylpropyl) formamide, which has been shown to diminish electroosmotic flow in glass microchannels by over 5 orders of magnitude. Finally, we describe the integration of the reported microfluidic fractionation device to a mass spectrometer via the electrospray ionization interface to allow inline label-free detection of analytes in our assay. Product purity greater than 95% has been accomplished using the SPLITT system presented here for a sample of peptides having the same electrical polarity.

ROS evaluation for a series of CNTs and their derivatives using an ESR method with DMPO.

Carbon nanotubes (CNTs) are important materials in advanced industries. It is a concern that pulmonary exposure to CNTs may induce carcinogenic responses. It has been recently reported that CNTs scavenge ROS though non-carbon fibers generate ROS. A comprehensive evaluation of ROS scavenging using various kinds of CNTs has not been demonstrated well. The present work specifically investigates ROS scavenging capabilities with a series of CNTs and their derivatives that were physically treated, and with the number of commercially available CNTs. CNT concentrations were controlled at 0.2 through 0.6 wt%. The ROS scavenging rate was measured by ESR with DMPO. Interestingly, the ROS scavenging rate was not only influenced by physical treatments, but was also dependent on individual manufacturing methods. Ratio of CNTs to DMPO/ hydrogen peroxide is a key parameter to obtain appropriate ROS quenching results for comparison of CNTs. The present results suggest that dangling bonds are not a sole factor for scavenging, and electron transfer on the CNT surface is not clearly determined to be the sole mechanism to explain ROS scavenging.

A rare skin adnexal gland tumour of the eyelid.

We report a rare and atypical skin adnexal tumour of the eyelid. We highlight this condition for clinicians who treat periocular neoplasia.

New Developments in the Understanding and Treatment of Autoimmune Hemolytic Anemia: Traditional and Novel Tests.

Careful consideration of the clinical history with traditional testing such as an antibody screen and direct antiglobulin test (DAT) allow for the categorization of most forms of autoimmune hemolytic anemia. Based on the initial findings, specialized testing can further categorize disease entities and increase the sensitivity of testing. In this section, we explain the diagnostic findings of both traditional and novel testing and how their appropriate interpretations help distinguish the forms of autoimmune hemolytic anemia (AIHA).

Orbital augmentation with injectable calcium hydroxylapatite for correction of postenucleation/evisceration socket syndrome.

PURPOSE: To demonstrate the utility of injectable calcium hydroxylapatite (Radiesse) for orbital volume augmentation to correct postenucleation/evisceration socket syndrome (PESS). METHODS: A retrospective chart review of all consecutive patients in our practice who received injectable calcium hydroxylapatite placed in the extraconal space to augment orbital volume was conducted. Patients with at least 6 months follow-up were included in the study. RESULTS: Among 26 patients with PESS who received injectable calcium hydroxylapatite for orbital volume augmentation, 15 individuals were identified with adequate follow-up. The mean amount of preoperative relative enophthalmos measured by Hertel exophthalmometry was 4 mm (range 0.5-7 mm). An average reduction of 2.4 mm of enophthalmos per syringe of filler was achieved. The mean follow-up obtained was 46 weeks (range 24-78 weeks). Most patients demonstrated clinical and aesthetic improvement that was observed to continue up to 1.5 years. Complications observed included anterior migration of filler, a peribulbar hemorrhage, and orbital discomfort. Two patients demonstrated little response to filler. CONCLUSIONS: Injectable calcium hydroxylapatite provides a novel, safe, simple, cost-effective technique to treat volume deficiency in the anophthalmic orbit. Augmentation achieved with this semipermanent filler has demonstrated a lasting effect in the orbit with little volume loss. Volume replacement can be titrated to the socket requirements. Correction of PESS using this technique may be limited in orbits that demonstrate significant fibrosis as a result of multiple surgeries, severe trauma, or radiation treatment.

Stereolithographic models to guide orbital and oculoplastic surgery.

PURPOSE: This paper aims to highlight the potential of stereolithographic models (SLM) as a tool in orbital surgical planning, and provides four examples of their role in facilitating successful surgery. METHOD: Retrospective case series report. RESULTS: Case 1: SLM facilitated a successful orbital biopsy of a deep orbital mass by allowing several practice trucut biopsies. Case 2: Complex orbital fracture-repair was facilitated by using a SLM to demonstrate post-trauma and previous post-surgical-intervention bony anatomy. Case 3: Replication of accurate orbital anatomy in a case of severe socket contracture facilitated the selection of Branemark-implant placement sites to prevent inadvertent entry into the cranial cavity. Case 4: SLM prevented unnecessary surgical intervention. CONCLUSION: SLM are useful tools for pre-operative surgical planning, and have applications in selected complex orbital and oculoplastic cases.

Assessment of temporal variations of natural radionuclides Beryllium-7 and Lead-212 in surface air in Tanay, Philippines.

Detection of radionuclides in surface air allows researchers to gain further insight on the behavior of radionuclides that may affect human radiation exposure especially in the event of a nuclear emergency. In this study, activity concentrations of naturally-occurring radionuclides Beryllium-7 (7Be) and Lead-212 (212Pb) in surface air and meteorological data collected in Tanay, Philippines from January 2012 to December 2017 were evaluated to determine the impact of atmospheric conditions and processes to airborne radioactivity. Surface air concentrations of 7Be and 212Pb were found to range from 0.00779 ±â€¯0.00188 to 11.2 ±â€¯0.116 mBq/m3 and from 1.371 ±â€¯0.036 to 106.6 ±â€¯1.075 mBq/m3, respectively. 7Be and 212Pb show distinct annual trends, suggesting that atmospheric conditions affect both radionuclides differently and independently. 7Be shows two peak concentrations annually, with the first peak occurring between January to April and the second lower peak occurring between October and November. 212Pb, on the other hand, shows annual peak concentrations occurring between April and June. Ambient temperature showed strong positive correlation with 212Pb concentration in surface air and a weak negative correlation with 7Be; relative humidity and precipitation showed varying degrees of negative correlation with radionuclide concentrations in surface air. Source locations for the unusually high 212Pb activity concentrations detected on 11-13 May 2013 and 19-31 May 2015 determined using WEB-GRAPE and HYSPLIT atmospheric transport models are presented as a case study. The data and findings of this study shall serve as basis for further studies on local and regional atmospheric transport and radiological impact assessment for the implementation of an effective nuclear and radiological emergency preparedness and response system in the country.

Upper eyelid myectomy in blepharospasm with associated apraxia of lid opening.

PURPOSE: To assess the impact of upper eyelid myectomy surgery on blepharospasm with associated apraxia of lid opening (ALO), dry eye, photophobia, and daily functioning in patients who are refractory to botulinum toxin treatment. DESIGN: Noncomparative, consecutive, interventional case series. METHODS: A retrospective chart review was performed to identify 100 consecutive patients beginning on January 1, 2000, who underwent upper eyelid myectomy surgery for blepharospasm and fulfilled the inclusion criteria. A survey was sent to all patients. Data were entered in an anonymous manner into a spreadsheet and analysis was performed using the Student t test with significance set at P<.05. RESULTS: Forty-five (88%) patients experienced ALO before surgery, among which 15 (33%) patients stated they were completely cured and 20 (44%) others had more than 50% improvement in ALO with surgery. In 20 of 30 patients who continued botulinum toxin treatment after surgery, the effect lasted longer. Twelve (29%) of 42 patients who experienced dry eyes before surgery improved. Eighteen (41%) of the 44 patients who experienced light sensitivity before surgery improved. Thirty-seven (82%) patients noted their cosmetic appearance to be better after surgery. The cumulative preoperative disability score was 14.11+/-5.78 (59%), whereas the cumulative postoperative disability score was 5.20+/-8.25 (22%; P<.01). CONCLUSIONS: Upper eyelid myectomy surgery appears to be effective in treating blepharospasm with associated ALO in most patients who are refractory to botulinum toxin injections and can provide improvement in the quality of life.

Phytochemical composition and metabolic performance-enhancing activity of dietary berries traditionally used by Native North Americans.

Four wild berry species, Amelanchier alnifolia, Viburnum trilobum, Prunus virginiana, and Shepherdia argentea, all integral to the traditional subsistence diet of Native American tribal communities, were evaluated to elucidate phytochemical composition and bioactive properties related to performance and human health. Biological activity was screened using a range of bioassays that assessed the potential for these little-known dietary berries to affect diabetic microvascular complications, hyperglycemia, pro-inflammatory gene expression, and metabolic syndrome symptoms. Nonpolar constituents from berries, including carotenoids, were potent inhibitors of aldose reductase (an enzyme involved in the etiology of diabetic microvascular complications), whereas the polar constituents, mainly phenolic acids, anthocyanins, and proanthocyanidins, were hypoglycemic agents and strong inhibitors of IL-1beta and COX-2 gene expression. Berry samples also showed the ability to modulate lipid metabolism and energy expenditure in a manner consistent with improving metabolic syndrome. The results demonstrate that these berries traditionally consumed by tribal cultures contain a rich array of phytochemicals that have the capacity to promote health and protect against chronic diseases, such as diabetes.

Adjuvant Therapies in Nonmetastatic Renal-Cell Carcinoma: A Review of the Literature.

To conduct a review of literature on adjuvant therapy in nonmetastatic renal-cell carcinoma (nmRCC) treated with nephrectomy and to describe the efficacy of adjuvant agents on cancer control outcomes. A review of the literature was performed in January 2018 to identify all studies evaluating adjuvant therapy in patients with nmRCC treated with nephrectomy using PubMed, Embase, Medline, and Cochrane Library databases. The following keywords were used: adjuvant therapy, renal-cell carcinoma, nonmetastatic, targeted molecular therapy, kidney cancer. The ClinicalTrials.gov website was queried to identify ongoing trials. Traditional adjuvant therapy agents consisted of interferon α, interleukin 2, autologous tumor cell vaccines, and monoclonal antibodies. None provided survival benefit. Three contemporary studies (S-TRAC, ASSURE, and PROTECT) using targeted therapy compared sunitinib to placebo (S-TRAC), sunitinib or sorafenib to placebo (ASSURE), and pazopanib to placebo (PROTECT), with controversial results. In contrast to ASSURE and PROTECT, S-TRAC demonstrated improved disease-free survival. Several trials that use checkpoint immunotherapy agents or vascular endothelial growth factor receptor tyrosine kinase inhibitors are ongoing. Many traditional therapies have shown no success as adjuvant therapy for nmRCC after nephrectomy. Targeted adjuvant therapy for nmRCC after nephrectomy showed controversial results, and its routine use is not currently endorsed.

Autologous dermis graft at the time of evisceration or enucleation.

AIM: To present a new technique using autologous dermis graft at the time of enucleation or evisceration to replace the ocular surface area lost when the corneal scleral button is excised. METHODS: A retrospective, interventional, non-comparative case series of patients who had an autologous dermis graft placed to assist in closure of Tenon's capsule and conjunctiva at the time of enucleation or evisceration. Medical records were reviewed and the following variables were recorded: age, sex, history of previous ocular surgery or radiation treatment, indication for surgery, type of surgery, laterality, type of orbital implant, size of implant, length of follow up, and complications. RESULTS: Nine patients were identified (three male, six female) Five had enucleation with implant placement and four had evisceration with implant placement. Four individuals received unwrapped porous polyethylene spherical implants, three received silicone implants, and two received hydroxylapatite implants. Follow up ranged from 30 to 112 weeks (mean (SD), 61 (28) weeks). No operative or early complications were observed. One patient who had enucleation after two rounds of brachytherapy for uveal melanoma developed subsequent late exposure of the implant. There were no complications involving the graft donor site. CONCLUSIONS: This small series shows that the use of a dermis graft is a safe and effective new technique to facilitate orbital rehabilitation. It is hypothesised that the extra surface area produced with a dermis graft preserves the fornices and allows a larger implant. It may also allow the implant to be placed more anteriorly which assists with both implant and prosthesis motility.

Injectable calcium hydroxylapatite for orbital volume augmentation.

OBJECTIVE: To describe a new method of augmenting orbital volume for anophthalmic enophthalmos correction. METHODS: A retrospective medical record review was conducted of 4 consecutive patients who had injectable calcium hydroxylapatite (Radiesse) placed in the extraconal space to augment orbital volume. RESULTS: Four patients were treated with 1 to 2 vials (1.3 mL per vial) of injectable calcium hydroxylapatite. The mean amount of preoperative enophthalmos measured by Hertel exophthalmometry was 4 mm (range, 2-7 mm). The mean follow-up was 57 weeks (range, 45-71 weeks). A reduction of enophthalmos, ranging from 2 to 5 mm (mean, 2.75 mm), was observed when comparing preoperative with postoperative measurements of the anophthalmic orbit with prosthesis in place. All patients demonstrated clinical and aesthetic improvement that was observed to continue at almost 1 year or more postoperatively. In one patient, injection was complicated by a peribulbar hemorrhage related to local anesthesia administration, which resolved without incident. CONCLUSIONS: Injectable calcium hydroxylapatite provides a new, safe, simple, cost-effective technique to treat volume deficiency in the anophthalmic orbit. Augmentation achieved with this semipermanent filler has demonstrated a lasting effect in the orbit of 1 year or more with little volume loss. The filler seems to last longer in areas with less movement, blood supply, and lymphatic drainage. Injection can even be performed in an office setting using local anesthesia. The amount of volume replacement can be titrated, and the procedure is repeatable until adequate volume is obtained.

A comparative evaluation of the anticancer properties of European and American elderberry fruits.

European elderberry (Sambucus nigra), recognized in Europe for its health-promoting properties for many generations, is known to contain a range of anthocyanins, flavonoids, and other polyphenolics that contribute to the high antioxidant capacity of its berries. American elderberry (Sambucus canadensis), on the other hand, has not been cultivated, bred, and promoted as a medicinal plant like its better-characterized European counterpart. In this study, aqueous acetone extracts of the berries from these two species were fractionated and tested in a range of assays that gauge anticarcinogenic potential. Both cultivated S. nigra and wild S. canadensis fruits demonstrated significant chemopreventive potential through strong induction of quinone reductase and inhibition of cyclooxygenase-2, which is indicative of anti-initiation and antipromotion properties, respectively. In addition, fractions of S. canadensis extract showed inhibition of ornithine decarboxylase, an enzyme marker related to the promotion stage of carcinogenesis. Analysis of active fractions using mass spectrometry and liquid chromatography-mass spectrometry revealed, in addition to flavonoids, the presence of more lipophilic compounds such as sesquiterpenes, iridoid monoterpene glycosides, and phytosterols.