Influence of urbanization of the western coast of the United Arab Emirates on trace metal content in muscle and liver of wild Red-spot emperor (Lethrinus lentjan).

We hypothesized that increased ambient concentrations of metals, as a consequence of escalating urbanization and industrialization of the Gulf region will respond in increased contamination of edible fish species. In this study, we report concentrations of chromium, manganese, cobalt, copper, zinc, arsenic, cadmium, mercury and lead in meat and liver of wild Red-spot emperor (Lethrinus lentjan) from three sampling points at the UAE coast. Analysis was performed by the ICP-MS/microwave digestion. Our study has shown that meat and liver metal content was significantly higher in areas with higher industrial activity, although metal values did not exceed permitted levels of fish for human consumption.     

A pilot study of home-based genetic testing completion rate in telegenetics cancer clinics in West Virginia Appalachia

Telegenetics has shifted some genetic testing performance to the patient's own home, with the patient collecting his/her own sample. Little is known regarding the rate of test completion of such home-based genetic testing. This study compared the completion rate of home-based genetic tests before and after a reminder system was implemented. In the pre-reminder group, we reviewed medical records for patients who were seen via telegenetics and agreed to complete genetic testing using an at-home test kit. In the reminder group, a prospective analysis of the genetic test completion rate was performed taking a clinical quality improvement approach where three reminders were provided for patients who had not submitted their at-home genetic testing. Our study included 94 patients' records: 46 pre-reminders and 48 reminders. The lab received 24 patient samples (52.2%) in the pre-reminder group. In the reminder group, 30 patients returned their kits (62.5%). Despite a higher percentage of patients completing their test in the reminder group, there was no statistically significant difference between the pre-reminder and reminder groups. The rate of test completion in our pilot test was statistically similar between the two groups, but the reminder group was trending toward a higher percent of completion which may be clinically meaningful.     

Proteinase activated receptor 2: Role of extracellular loop 2 for ligand-mediated activation

1. Rat proteinase-activated receptor-2 (PAR2) variants were stably expressed in rat KNRK cells: (a) wild-type (wt) - PAR2; (b) PAR2PRR, with the extracellular loop 2 (EL-2) sequence P231E232E233mutated to PRR and (c) PAR2NET, with the EL-2 sequence, PEEV changed to NETL. Cell lines were evaluated for their sensitivity (calcium signalling) towards trypsin and the receptor-activating peptides, SLIGRL-NH2, SLIGEL-NH2, trans-cinnamoyl(tc)-LIGRLO-NH2, and SFLLR-NH2. 2. SLIGEL-NH2 exhibited low potency (1 : 200 relative to SLIGRL-NH2) in wild-type PAR2. Its activity was increased 5 fold in PAR2PRR, but it was inactive in PAR2NET. 3. In PAR2PRR, the potencies of SLIGRL-NH2, tc-LIGRLO-NH2, and SFLLR-NH2 were decreased by 80 - 100 fold. But, the potency of trypsin was decreased by only 7 fold. 4. In PAR2NET, highly homologous in EL-2 with proteinase-activated receptor-1 (PAR1), the potency of the PAR1-derived peptide, SFLLR-NH2, was reduced by 100 fold compared with wt-PAR2, whereas the potency of the PAR2-derived AP, SLIGRL-NH2 was reduced 10 fold. In contrast, the potency of trypsin in PAR2NET was almost the same as in wt-PAR2. 5. We conclude that the acidic EL-2 tripeptide, PEE, in PAR2 plays an important role in governing agonist activity. 6. The data obtained with the PEEV-->NETL mutation suggested: (a) that SLIGRL-NH2 and SFLLR-NH2 interact in a distinct manner with PAR2 and (b) that SFLLR-NH2 may interact differently with PAR2 than it does with PAR1. 7 The differential reductions in the potencies of SLIGRL-NH2, compared with trypsin in the PAR2PRR and PAR2NET cell lines point to differences between the interactions of the trypsin-revealed tethered ligand and the free receptor-activating peptide with PAR2.     

Various aspects of hearing loss in newborns: A narrative review

Hearing loss is considered the most common birth defect. The estimated prevalence of moderate and severe hearing loss in a normal newborn is 0.1%-0.3%, while the prevalence is 2%-4% in newborns admitted to the newborn intensive care unit. Neonatal hearing loss can be congenital (syndromic or non-syndromic) or acquired such as ototoxicity. In addition, the types of hearing loss can be conductive, sensorineural, or mixed. Hearing is vital for the acquisition of language and learning. Therefore, early detection and prompt treatment are of utmost importance in preventing the unwanted sequel of hearing loss. The hearing screening program is mandatory in many nations, especially for high-risk newborns. An automated auditory brainstem response test is used as a screening tool in newborns admitted to the newborn intensive care unit. Moreover, genetic testing and screening for cytomegalovirus in newborns are essential in identifying the cause of hearing loss, particularly, mild and delayed onset types of hearing loss. We aimed to update the knowledge on the various aspects of hearing loss in newborns with regard to the epidemiology, risk factors, causes, screening program, investigations, and different modalities of treatment.     

Is Use of BMP-2 Associated with Tumor Growth and Osteoblastic Differentiation in Murine Models of Osteosarcoma?

BackgroundThe putative benefit of rhBMP-2 is in the setting of limb reconstruction using structural allografts, whether it be allograft-prosthetic composites, osteoarticular allografts, or intercalary segmental grafts. There are also potential advantages in augmenting osseointegration of uncemented endoprosthetics and in reducing infection. Recombinant human BMP-2 might mitigate nonunion in structural allograft augmented osteosarcoma limb salvage surgery; however, its use is limited because of concerns about the prooncogenic effects of the agent.Questions/purposes(1) To assess if BMP-2 signaling influences osteosarcoma cell line growth. (2) To characterize degree of osteosarcoma cell line osteoblastic differentiation in response to BMP-2. (3) To assess if BMP-2 signaling has a consistent effect on local or systemic tumor burden in various orthotopic murine models of osteosarcoma.MethodsIn this study, 143b, SaOS-2 and DLM8-M1 osteosarcoma cell lines were transfected with BMP-2 cDNA controlled by a constitutive promoter (experimental) or an empty vector (control) using a PiggyBac transposon system. Cellular proliferation was assessed using a quantitative MTT colorimetric assay. Osteoblastic differentiation was compared between control and experimental cell lines using quantitative real-time polymerase chain reaction of the osteoblastic markers connective tissue growth factor, Runx-2, Osterix, alkaline phosphatase and osteocalcin. Experimental and control cell lines were injected into the proximal tibia of either NOD-SCID (143b and SaOS-2 xenograft model), or C3H (DLM8-M1 syngeneic model) mice. Local tumor burden was quantitatively assessed using tumor volume caliper measurements and bioluminescence, and qualitatively assessed using post-mortem ex vivo microCT. Lung metastasis was qualitatively assessed by the presence of bioluminescence, and incidence was confirmed using histology. rhBMP-2 soaked absorbable collagen sponges (experimental) and sterile-H₂O soaked absorbable collagen sponges (control) were implanted adjacent to 143b proximal tibial cell line injections to compare the effects of exogenous BMP-2 application with endogenous upregulation.ResultsConstitutive expression of BMP-2 increased the in vitro proliferation of 143b cells (absorbance values 1.2 ± 0.1 versus 0.89 ± 0.1, mean difference 0.36 [95% CI 0.12 to 0.6]; p = 0.01), but had no effect on SaOS-2 and DLM8-M1 cell proliferation. In response to constitutive BMP-2 expression, 143b cells had no differences in osteoblastic differentiation, while DLM8-M1 cells downregulated the early marker connective tissue growth factor (mean ΔCt 0.2 ± 0.1 versus 0.6 ± 0.1; p = 0.002) and upregulated the early-mid range marker Runx-2 (mean ΔCt -0.8 ± 0.1 versus -1.1 ± 0.1; p = 0.002), and SaOS-2 cells upregulated the mid-range marker Osterix (mean ΔCt -2.1 ± 0.6 versus -3.9 ± 0.6; p = 0.002). Constitutive expression of BMP-2 resulted in greater 143b and DLM8-M1 local tumor volume (143b: 307.2 ± 106.8 mm³ versus 1316 ± 387.4 mm³, mean difference 1009 mm³ [95% CI 674.5 to 1343]; p < 0.001, DLM8-M1 week four: 0 mm³ versus 326.1 ± 72.8 mm³, mean difference 326.1 mm³ [95% CI 121.2 to 531]; p = 0.009), but modestly reduced local tumor growth in SaOS-2 (9.5 x 10⁸ ± 8.3x10⁸ photons/s versus 9.3 x 10⁷ ± 1.5 x 10⁸ photons/s, mean difference 8.6 x 10⁸ photons/s [95% CI 5.1 x 10⁸ to 1.2 x 10⁹]; p < 0.001). Application of exogenous rhBMP-2 also increased 143b local tumor volume (495 ± 91.9 mm³ versus 1335 ± 102.7 mm³, mean difference 840.3 mm³ [95% CI 671.7 to 1009]; p < 0.001). Incidence of lung metastases was not different between experimental or control groups for all experimental conditions.ConclusionsAs demonstrated by others, ectopic BMP-2 signaling has unpredictable effects on local tumor proliferation in murine models of osteosarcoma and does not consistently result in osteosarcoma cell line differentiation. Further investigations into other methods of safe bone and soft tissue healing augmentation and the use of differentiation therapies is warranted.Clinical RelevanceOur results indicate that BMP-2 has the potential to stimulate the growth of osteosarcoma cells that are poorly responsive to BMP-2 mediated osteoblastic differentiation. As this differentiation potential is unpredictable in the clinical setting, BMP-2 may promote the growth of microscopic residual tumor burden after resection. Our study provides further support for the recommendation to avoid the use of BMP-2 after limb-salvage surgery in patients with osteosarcoma.     

Potency following conformal neutron/photon irradiation for localized prostate cancer

: To assess the effect of conformal neutron/photon irradiation with or without neoadjuvant hormonal therapy on posttreatment potency.

: Seventy-six patients with localized adenocarcinoma of the prostate, Stage T1 or T2 N0 Mo, Gleason score ≤7, were enrolled on a prospective Phase II study. Each patient received 9–10 Neutron + 38 Photon Gy. Twenty-eight patients received neoadjuvant hormonal therapy in conjunction with radiation therapy. Potency was assessed prior to starting treatment and was assessed at each subsequent follow-up visit.

: Fifty-two of 75 patients (70%) were potent at the start of therapy. Thirty-eight of 52 (73%) had functional erections and 14 of 52 (27%) had erections termed nonfunctional, which were of insufficient strength for intercourse. After treatment, 35 of 52 (67%) retained potency. Twenty-nine of 38 (76%) with functional erections pretreatment maintained this ability. Only 6 of 14 patients (43%) with nonfunctional erection pretreatment maintained their level of potency. Neoadjuvant hormonal therapy did not impact on the ability to maintain erections. Sixty-five percent of those patients receiving hormones retained erectile function, while 69% of those who did not receive hormones maintained erectile function. Age was not a significant factor in posttreatment potency, although a trend towards potency in younger patients was observed . (p = 0.74).

: The majority (67%) of patients maintained their level of erectile function following conformal sequential neutron photon irradiation. This comparable to that achieved with photon irradiation alone. No significant change in potency was seen with neoadjuvant hormonal therapy or with increasing patient age.