YAP insertion signature in South Asia

A total of 2169 samples from 21 tribal populations from different regions of India were scanned for the Y-chromosome Alu polymorphism. This study reports, for the first time, high frequencies (8-65%) of Y Alu polymorphic (YAP) insertion in northeast Indian tribes. All seven Jarawa samples from the Andaman and Nicobar islands had the YAP insertion, in conformity with an earlier study of Andaman Islanders. One isolated case with haplotype E* was found in Dungri Bhill, a western Indian population, while YAP insertion in northeast India and Andaman tribes was found in association with haplotype D* (M168, M174). YAP insertion frequencies reported in the mainland Indian populations are negligible, according to previous studies. Genetic drift may be the causative factor for the variable frequency of the YAP insertion in the mainland populations, while the founder effect may have resulted in the highest incidence of haplotype D among the Andaman Islanders. The results of YAP insertion and the evidence of previous mtDNA studies indicate an early out of Africa migration to the Andaman and Nicobar Islands. The findings of YAP insertion in northeast Indian tribes are very significant for understanding the evolutionary history of the region.     

Intradermal Delivery of a Near-Infrared Photosensitizer Using Dissolving Microneedle Arrays

Nodular basal cell carcinoma is a deep skin lesion and one of the most common cancers. Conventional photodynamic therapy is limited to treatment of superficial skin lesions. The parenteral administration of near-IR preformed photosensitizers suffers from poor selectivity and may result in prolonged skin photosensitivity. Microneedles (MNs) can provide localized drug delivery to skin lesions. Intradermal delivery of the preformed near-IR photosensitizer; 5,10,15,20-tetrakis(2,6-difluoro-3-N-methylsulfamoylphenyl bacteriochlorin (Redaporfin?) using dissolving MN was successful in vitro and in vivo. MN demonstrated complete dissolution 30 min after skin application and showed sufficient mechanical strength to penetrate the skin to a depth of 450 μm. In vitro deposition studies illustrated that the drug was delivered and detected down to 5 mm in skin. In vivo biodistribution studies in athymic nude mice Crl:NU(NCr)-Foxn1^nu showed both fast initial release and localized drug delivery. The MN-treated mice showed a progressive decrease in the fluorescence intensity at the application site over the 7-day experiment period, with the highest and lowest fluorescence intensities measured being 9.2 × 10¹⁰ ± 2.5 × 10¹⁰ and 3.8 × 10⁹ ± 1.6 × 10⁹ p/s, respectively. By day 7, there was some migration of fluorescence away from the site of initial MN application. However, the majority of the body surfaces showed fluorescence levels that were comparable to those seen in the negative control group. This work suggests utility for polymeric MN arrays in minimally invasive intradermal delivery to enhance photodynamic therapy of deep skin lesions.     

Diagnosing COVID-19 in human serum using Raman spectroscopy

Lasers in Medical Science - This study proposed the diagnosis of COVID-19 by means of Raman spectroscopy. Samples of blood serum from 10 patients positive and 10 patients negative for...     

Pharmacist consultations in general practice clinics: The Pharmacists in Practice Study (PIPS)

BackgroundMedication-related problems (MRPs) are a concern in primary care settings. Pharmacists based in the community or community pharmacies are able to identify, resolve and prevent MRPs; however, the lack of a formal partnership with physicians and poor access to patients' medical records are limitations. In Australia, delivery of pharmacist services within general practice clinics is rare.ObjectivesTo evaluate the effectiveness of consultations by pharmacists based within primary care medical practices.MethodsA prospective, before-after intervention study was conducted at two primary health care (general practice) clinics in Melbourne, Australia. Participants were clinic patients who had risk-factors for MRPs (e.g. polypharmacy). Patients received a consultation with the pharmacist in a private consulting room at the clinic or in their home. The pharmacist reviewed the patient's medication regimen and adherence, with full access to their medical record, provided patient education, and produced a report for the general practitioner. The primary outcome was the number of MRPs identified by the pharmacist, and the number that remained unresolved 6 months after the pharmacist consultation. Secondary outcomes included medication adherence, health service use, and patient satisfaction.ResultsEighty-two patients were recruited and 62 (75.6%) completed the study. The median number of MRPs per patient identified by the practice pharmacist was 2 (interquartile range [IQR] 1, 4). Six months after review, this fell to 0 (IQR 0, 1), P < 0.001. The proportion of patients who were adherent to their medications improved significantly, according to both the Morisky (44.1% versus 62.7%, P = 0.023) and the Tool for Adherence Behaviour Screening (TABS) (35.6% versus 57.6%, P = 0.019) scales. There was no significant effect on health service use. Patients were highly satisfied with the pharmacist consultations.ConclusionsConsultations undertaken by pharmacists located within primary health care clinics were effective in identifying and resolving MRPs. The consultations were well received by patients and were associated with improvements in medication adherence.     

Epidemiology of musculoskeletal upper extremity ambulatory surgery in the United States

Background

Musculoskeletal disorders of the upper extremity are common reasons for patients to seek care and undergo ambulatory surgery. The objective of our study was to assess the overall and age-adjusted utilization rates of rotator cuff repair, shoulder arthroscopy performed for indications other than rotator cuff repair, carpal tunnel release, and wrist arthroscopy performed for indications other than carpal tunnel release in the United States. We also compared demographics, indications, and operating room time for these procedures.

Methods

We used the 2006 National Survey of Ambulatory Surgery to estimate the number of procedures of interest performed in the United States in 2006. We combined these data with population size estimates from the 2006 U.S. Census Bureau to calculate rates per 10,000 persons.

Results

An estimated 272,148 (95% confidence intervals (CI)?=?218,994, 325,302) rotator cuff repairs, 257,541 (95% CI?=?185,268, 329,814) shoulder arthroscopies excluding those for cuff repairs, 576,924 (95% CI?=?459,239, 694,609) carpal tunnel releases, and 25,250 (95% CI?=?17,304, 33,196) wrist arthroscopies excluding those for carpal tunnel release were performed. Overall, carpal tunnel release had the highest utilization rate (37.3 per 10,000 persons in persons of age 45–64 years; 38.7 per 10,000 persons in 65–74 year olds, and; 44.2 per 10,000 persons in the age-group 75 years and older). Among those undergoing rotator cuff repairs, those in the age-group 65–74 had the highest utilization (28.3 per 10,000 persons). The most common indications for non-cuff repair related shoulder arthroscopy were impingement syndrome, periarthritis, bursitis, and instability/SLAP tears. Non-carpal tunnel release related wrist arthroscopy was most commonly performed for ligament sprains and diagnostic arthroscopies for pain and articular cartilage disorders.

Conclusions

Our data shows substantial age and demographic differences in the utilization of these commonly performed upper extremity ambulatory procedures. While over one million upper extremity procedures of interest were performed, evidence-based clinical indications for these procedures remain poorly defined.     

Genotoxicity evaluation of nanosized titanium dioxide,synthetic amorphous silica and multi-walled carbon nanotubes in human lymphocytes

Toxicological characterization of manufactured nanomaterials (NMs) is essential for safety assessment, while keeping pace with innovation from their development and application in consumer products. The specific physicochemical properties of NMs, including size and morphology, might influence their toxicity and have impact on human health. The present work aimed to evaluate the genotoxicity of nanosized titanium dioxide (TiO₂), synthetic amorphous silica (SAS) and multiwalled carbon nanotubes (MWCNTs), in human lymphocytes. The morphology and size of those NMs were characterized by transmission electron microscopy, while the hydrodynamic particle size-distributions were determined by dynamic light scattering. Using a standardized procedure to ensure the dispersion of the NMs and the cytokinesis-block micronucleus assay (without metabolic activation), we observed significant increases in the frequencies of micronucleated binucleated cells (MNBCs) for some TiO₂ NMs and for two MWCNTs, although no clear dose–response relationships could be disclosed. In contrast, all forms of SAS analyzed in this study were unable to induce micronuclei. The present findings increase the weight of evidence towards a genotoxic effect of some forms of TiO₂ and some MWCNTs. Regarding safety assessment, the differential genotoxicity observed for closely related NMs highlights the importance of investigating the toxic potential of each NM individually, instead of assuming a common mechanism and equal genotoxic effects for a set of similar NMs.     

黄芩苷衍生物的合成及其生物活性研究

目的为改善黄芩苷的溶解性,设计合成系列黄芩苷衍生物,并评价其抗脂质过氧化活性和抗肿瘤活性。方法以黄芩苷和环氧乙(丙)烷为原料,通过羟乙基化、羟丙基化、酯化反应合成了一系列黄芩苷衍生物;分别采用生化法和台盼蓝染色法测试目标化合物对小鼠脑脂质过氧化产物丙二醛(MDA)的体外抑制作用及对白血病细胞HL-60的生长抑制活性。结果合成了13个黄芩苷衍生物,其结构经1H-NMR和MS确证。其中,化合物3⁶、116、11¹3为未见文献报道的新化合物。化合物1、6对MDA的抑制作用显著,化合物713为未见文献报道的新化合物。化合物1、6对MDA的抑制作用显著,化合物7¹0、12具有中等强度的抑制HL-60生长作用。结论黄芩苷结构中的酚羟基是其抑制脂质过氧化产物MDA的活性基团,葡萄糖醛酸的6位游离羧基是能够增强化合物抗肿瘤活性的有效基团。     

Serum glutathione-S-transferase and glutathione reductase activity in head and neck cancer patients

Glutathione, an antioxidant plays an important role in phase-II detoxification of carcinogens. The levels of reduced glutathione are maintained by glutathione-depleting as well as replenishing enzymes such as glutathione-s-transferase (GST) and glutathione reductase (GR), respectively. Pre and post treatment changes in GST and GR activities in head and neck cancer patients were analysed. Serum GST and GR were analysed from untreated head and neck cancer patients (PT) (n=146), controls with habit of tobacco (VHT) (n=25) as well as without (no) habit of tobacco (NHT) (n=25) and patients with oral precancerous conditions (OPC) (n=50). The cancer patients were followed-up after initiation of anticancer therapy. Follow-up blood samples were collected. Serum GST and GR activities were estimated by highly sensitive and specific spectrophotometric methods. Untreated cancer patients showed elevated mean serum GST and GR activities as compared to NHT. Patients with OPC had declined mean GST activity as compared to WHT and untreated cancer patients. Paired t-test revealed that complete responders (CR) showed significantly elevated GST levels and declined GR activities (p < 0.001) as compared to those in PT. No correlation was found between stage of the disease and GST, GR activity. Paired t-test showed significant decreased in GR activity in nonresponders (NR) treated with radiotherapy (p=0.01). The study suggested that analysis of glutathione and glutathione-depleting enzymes can be helpful for treatment monitoring of head and neck cancer patients.     

Few colonies of the host Bombus terrestris disproportionately affect the genetic diversity of its parasite,Crithidia bombi

Sex and recombination have long been considered as necessary means for hosts to keep up with and resist to their faster reproducing parasites. On the other hand, comparatively little attention has been paid to potential benefits of recombination for the parasites. Using as model organisms the bumblebee Bombus terrestris and its genetically highly variable trypanosomatid parasite Crithidia bombi we analysed the infection dynamics as well as the relative frequency of parasite recombinants over time, in colonies that were either immune-challenged with heat-killed bacteria or sham-inoculated. In addition, we used infective cells from a given colony to infect workers from other, untreated colonies, to investigate whether recombinant parasite strains may have a competitive advantage over the parental strains to infect the surrounding host population. We show that in our experimental setup the host immune status does not influence the proportion of recombinant parasite cells in the infection. Neither do recombinant parasite strains have an advantage over the parental ones at infecting workers unrelated to the host colony the infection originally came from. However, we found that the prevalence of recombinants was highly variable among colonies, with one particular colony producing significantly more recombinant strains than others. As the successful infection of daughter queens – the only individuals surviving the winter to the next year – is proportional to the number of circulating parasite strains in the colony, we suggest that such “super-producing” colonies may be responsible for most of the infections happening in the next year.