Structure determination by cryoEM at 100 keV.

Electron cryomicroscopy can, in principle, determine the structures of most biological molecules but is currently limited by access, specimen preparation difficulties, and cost. We describe a purpose-built instrument operating at 100 keV-including advances in electron optics, detection, and processing-that makes structure determination fast and simple at a fraction of current costs. The instrument attains its theoretical performance limits, allowing atomic resolution imaging of gold test specimens and biological molecular structure determination in hours. We demonstrate its capabilities by determining the structures of eleven different specimens, ranging in size from 140 kDa to 2 MDa, using a fraction of the data normally required. CryoEM with a microscope designed specifically for high-efficiency, on-the-spot imaging of biological molecules will expand structural biology to a wide range of previously intractable problems.

A scanning-to-incision switch in TFIIH-XPG induced by DNA damage licenses nucleotide excision repair.

Nucleotide excision repair (NER) is critical for removing bulky DNA base lesions and avoiding diseases. NER couples lesion recognition by XPC to strand separation by XPB and XPD ATPases, followed by lesion excision by XPF and XPG nucleases. Here, we describe key regulatory mechanisms and roles of XPG for and beyond its cleavage activity. Strikingly, by combing single-molecule imaging and bulk cleavage assays, we found that XPG binding to the 7-subunit TFIIH core (coreTFIIH) stimulates coreTFIIH-dependent double-strand (ds)DNA unwinding 10-fold, and XPG-dependent DNA cleavage by up to 700-fold. Simultaneous monitoring of rates for coreTFIIH single-stranded (ss)DNA translocation and dsDNA unwinding showed XPG acts by switching ssDNA translocation to dsDNA unwinding as a likely committed step. Pertinent to the NER pathway regulation, XPG incision activity is suppressed during coreTFIIH translocation on DNA but is licensed when coreTFIIH stalls at the lesion or when ATP hydrolysis is blocked. Moreover, ≥15 nucleotides of 5'-ssDNA is a prerequisite for efficient translocation and incision. Our results unveil a paired coordination mechanism in which key lesion scanning and DNA incision steps are sequentially coordinated, and damaged patch removal is only licensed after generation of ≥15 nucleotides of 5'-ssDNA, ensuring the correct ssDNA bubble size before cleavage.

Nucleotide excision repair (NER) removes bulky DNA lesions and is thereby crucial in maintaining transcription and genomic integrity. Here, the authors show a dual function for the XPG nuclease that is critical for finding and excising the damage. During the separation of the damage-containing strand from the undamaged strand, XPG stimulates TFIIH dependent dsDNA unwinding 10 fold. In return, when TFIIH stalls at the damage it stimulates XPG nuclease activity 700 fold. Remarkably, this mutually exclusive coordination requires a bubble longer than 15 nucleotides. This study addressees why a bubble of a certain size is needed to facilitate NER and why XPG is recruited at the beginning of NER when its endonucleolytic activity is required at the very end.

Current alternatives to traditional radial approach for coronary interventions: A randomized prospective study of the ulnar and distal radial approaches.

BACKGROUND: The radial artery is the standard access for coronary intervention; however, it is essential to have alternative accesses as it may be used as a conduit during coronary artery bypass grafting or for dialysis fistula. Ulnar and distal radial artery accesses have emerged as alternative accesses for traditional radial artery. AIM: To compare distal radial artery access and ulnar artery access as alternatives to traditional radial artery access regarding safety, efficacy, and success rate. METHODS: Two-hundred patients were included (100 traditional radial [TRA], 50 distal radial [DRA] and 50 ulnar). Access artery follow up ultrasound was performed up to 28 days. RESULTS: Procedural success rate was 97%, 74%, and 92% in the TRA, DRA and ulnar groups, respectively (p < 0.001). Crossover occurred in 3 patients (3%) in TRA, 13 patients (26%) in DRA and 4 cases (8%) in ulnar group (p < 0.001). The most common cause of crossover was failure of artery cannulation. Regarding cannulation time, the mean access time in seconds was 80.19 ± 25.98, 148.4 ± 29.60, 90.5 ± 21.84 in TRA, DRA and ulnar groups, respectively (p < 0.001). CONCLUSIONS: Our study concluded that these new approaches proved to be potential alternatives to traditional radial approach; however, ulnar artery access proved to be superior to distal radial artery access as regards success rate and cannulation time.

Fresh osteochondral allograft transplantation for knee full-thickness articular cartilage lesions using femoral head of living donors: short-term results.

BACKGROUND: Fresh osteochondral allograft transplantation is a good treatment option of cartilage defects. However, this treatment option is not available in all countries due to limited graft availability and tissue banks limitations. The purpose of this study is to assess the short term functional and imaging outcomes of fresh osteochondral allograft transplantation in the knee using the femoral head of living donors. HYPOTHESIS: Fresh osteochondral allografts from the femoral heads of living donors is a valid graft source for management of distal Femur cartilage defects. This technique can improve functional knee scores with good radiological outcomes. STUDY DESIGN: Prospective case series. METHODS: Fifteen patients with full thickness cartilage defects of the distal femur underwent osteochondral allograft transplantation from the femoral heads of living donors. Grafts were transplanted by both shell and multiple dowels techniques. The average follow up duration was 18.3 months (range, 12-25 months). Patients were evaluated by Lysholm and International Knee Documentation Committee (IKDC) scores, radiography and MR imaging using Osteochondral Allograft MRI Scoring System (OCAMRISS). RESULTS: There was a statistically significant improvement (P < 0.001) in both Lysholm and IKDC average scores at 6 months and 12 months postoperative. Postoperative MRI was done at an average 6.8 months (range, 5-11 months) postoperative. The mean total OCAMRISS score was 3.4 (range, 1-7). A second look arthroscopy was done in four patients and showed intact articular cartilage in all three patients. CONCLUSION: Femoral head of living donors is a valid new source for fresh osteochondral allograft transplantation of knee osteochondral lesions. Short term results showed improvement in clinical assessment scores. Follow up imaging showed graft incorporation and good MRI scores.

Analysis of the Facial Measurements and Dental Arch Dimensions for the Construction of Dental Prostheses among Adult Yemenis.

AIM: To investigate the dental arch dimension (width, length, and height) and facial measurements including inner-canthal width (ICW), bizygomatic width (BZW), inter-alar width (IAW), and mouth width (MW), and to assess the correlation between these facial measurements and dental arch width (canine width [CW], inter-first premolar width [I1PW], and inter-first molar width [I1MW]), to establish a preliminary reference for artificial teeth selection in Yemeni adult. MATERIALS AND METHODS: The study included 80 individuals (40 males and 40 females) with symmetrical faces and normal class I occlusion ranging in age from 20 to 35. Maxillary and mandibular stone casts were made for each individual. The dimensions of dental casts and facial measurements, including ICW, BZW, IAW, and MW, were assessed using a digital caliper. The collected data were analyzed by using the SPSS software program. The descriptive statistics for each measurement were made. Differences between males and females were tested using an independent-sample t-test with p-values below 0.05 considered significant. Pearson correlation coefficient between facial measurements and dental arch width was also done. RESULTS: Most dental arch dimensions and facial measurements exhibited larger mean values in the male than in the female group, with the greatest significant difference in the maxillary dental arch width and the lowest in mandibular dental arch length. A highly significant correlation is observed between ICW and maxillary canine width (CW) (r = 0.318, p = 0.004). In contrast, no significant correlation between dental arch width and BZW, IAW, and MW is shown. CONCLUSIONS: Within this study's limitations, the ICW can determine the ideal dimension of the artificial teeth in the anterior maxillary arch. While the other facial parameters, including BZW, IAW, and MW, cannot be used for artificial teeth selection in Yemeni populations. CLINICAL SIGNIFICANCE: The findings of this study established a reference database of facial measurements and their correlation to dental arch and teeth width in Yemeni populations. So, it can be implemented in artificial teeth and dental prostheses design and construction.

A Radiographic Study of the Root-to-Crown Ratio of Natural Permanent Teeth in 81 Saudi Adults.

BACKGROUND The ratio between a tooth root and its crown is an essential diagnostic parameter that determines treatment options. This radiographic study used panoramic dental radiographs or orthopantograms to measure the mean root (R)-to-crown (C) ratios (R/C) of the permanent teeth in 81 Saudi adults. MATERIAL AND METHODS A total of 81 panoramic radiographs of Saudi adult patients (40 males and 41 females) previously treated in the College of Dentistry, Saudi Arabia, aged 16-35 years, were selected. The crown height and root length for each tooth were measured on the digital panoramic radiographs. The correlation coefficient (intra-class) was calculated to assess the intra-examiner reproducibility and a good agreement was achieved (ICC=0.79-0.89). RESULTS For both males and females, the highest mean R/C ratio was for maxillary canine (1.91) and for mandibular second premolar (2.0) while the lowest R/C ratio was for maxillary first molar (1.64) and for mandibular central incisor (1.59). Except for the maxillary second premolar, no significant differences in R/C ratios were observed for maxillary arch. In the mandibular arch, the R/C ratio for lateral incisor, both premolars, and molars differed significantly (P<0.05). Among males, statistically significant differences between teeth existed in R/C ratios for central and lateral incisors, second premolar, and both molars (P>0.05). For females, significant differences between teeth in R/C ratios were observed for both premolars and both molars (P>0.05). CONCLUSIONS This study supports the findings from previous studies that orthopantograms can be used to calculate root/crown ratios, which varies between males and females and the dental arch among Saudi adults.

Discovery of new 1H-pyrazolo[3,4-d]pyrimidine derivatives as anticancer agents targeting EGFRWT and EGFRT790M.

New 1H-pyrazolo[3,4-d]pyrimidine derivatives were designed and synthesised to act as epidermal growth factor receptor inhibitors (EGFRIs). The synthesised derivatives were assessed for their in vitro anti-proliferative activities against A549 and HCT-116 cancer cells. Compounds 8, 10, 12a, and 12b showed potent anti-proliferative activities. Compound 12b was the most promising member with IC50 values of 8.21 and 19.56 µM against A549 and HCT-116, respectively. Compounds 8, 10, 12a, and 12b were evaluated for their kinase inhibitory activities against wild EGFR (EGFRWT). Compound 12b was the most potent member showing an IC50 value of 0.016 µM. In addition, compound 12b showed noticeable activity against mutant EGFR (EGFRT790M) (IC50 = 0.236 µM). Flow cytometric analyses revealed that compound 12b is a good apoptotic inducer and can arrest the cell cycle at S and G2/M phases. Furthermore, it produced an 8.8-fold increase in BAX/Bcl-2 ratio. Molecular docking studies were carried out against EGFRWT and EGFRT790M.

Positive Influences of Ohmicsonication on Phytochemical Profile and Storage Stability of Not-from-Concentrate Mango Juice.

Processing technique and storage conditions are the main factors that affect the phytochemical profile of Not-from-Concentrate (NFC) juice, which could decrease the nutritional and bioactive properties of the corresponding juice. The aim of this study was to evaluate the quality changes that occurred in NFC mango juice after Ohmicsonication (OS) and during storage in comparison to other processing methods such as sonication (S), thermosonication (TS), ohmic heating (OH), and conventional heating (CH). Quality attributes such as polyphenoloxidase (PPO) and pectinmethylesterase (PME) activities, ascorbic acid and hydroxymethyl furfural (HMF) contents, total phenolics, total flavonoids, total carotenoids, electric conductivity, color values and microbial load (total plate count, mold, yeast, and psychrophilic bacteria) were examined. OS and OH treatments demonstrated the highest inactivation of PPO (100%), while CH and TS displaying inhibitions 89% and 90%, respectively and only S treatment exhibited insufficient inactivation of both PPO and microbial load. However, the inhibition of PME followed the order OS (96.5%) > OH (94.9%) > TS (92.5%) > CH (88.5%). The best treatment, with the highest retention of phytochemical contents (ascorbic acid, total carotenoids, antioxidant activity, total flavonoids, and total phenolic content) for NFC mango juice and during storage was obtained with OS treated samples compared to other treatments (in the order from the lowest to highest percentage, OS < OH < TS < CH). Consequently, the results indicated that OS could be applied as a new mild thermal treatment in the production of mango juice with improved quality properties of stored NFC mango juice.

Design, Synthesis, biological Evaluation, and molecular docking studies of novel Pyrazolo[3,4-d]Pyrimidine derivative scaffolds as potent EGFR inhibitors and cell apoptosis inducers.

A series of novel hybrid pyrazolo[3,4-d]pyramidine derivatives was designed and chemically synthesized in useful yields. The synthesized compounds were structurally characterized by the usual techniques. All the new synthesized compounds were biologically screened in vitro for their antiproliferative activities against a panel of four cancer cell lines, namely HepG-2, MCF-7, HCT-116, and Hela. The results of cytotoxic evaluation indicated that compound 14d was appeared to be the most prominent broad-spectrum cytotoxic activity and significantly more potent than sorafenib with IC50 values of 4.28, 5.18, 3.97, and 9.85 µM against four cell lines (HePG2, Hela, HCT-116 and MCF-7). In addition, compound 15 was displayed promising antiproliferative effect against all tested cell lines with IC50 value less than 11 µM compared with sorafenib as a control drug. Besides, structurally pharmacophoric features indicated that pyrazolo[3,4-d]pyrimidine scaffold having an amide linker and substituted with phenyl moiety at the 5-position was more potent than those possessing azomethine methyl, azomethine proton and carbomethene linkers, which lead to significant decrease in antiproliferative activity. The most potent compounds were further selected and evaluated for their activities against epidermal growth factor receptor (EGFR) kinase inhibitors according to homogenous time resolved fluorescence (HTRF) assay. The most potent compound 14d exhibited the most promising inhibitory activity against EGFRWT with IC50 value of 56.02 ± 1.38 µM compared with gefitinib as control drug with IC50 value of 41.79 ± 1.07 µM. Moreover, the inhibition of cell cycle progression and induction of apoptosis in the A549 cell line at G2/M and pre-G1 phases of cell cycle might contribute to cancer treatment that evaluated by Annexin V-FITC/PI double staining detection method. Finally, molecular docking studies were conducted to investigate that probable binding conformations of these anticancer agents and ADME properties were calculated to predict pharmacokinetics and toxic properties of the target compounds.

Replisome speed determines the efficiency of the Tus-Ter replication termination barrier.

In all domains of life, DNA synthesis occurs bidirectionally from replication origins. Despite variable rates of replication fork progression, fork convergence often occurs at specific sites. Escherichia coli sets a 'replication fork trap' that allows the first arriving fork to enter but not to leave the terminus region. The trap is set by oppositely oriented Tus-bound Ter sites that block forks on approach from only one direction. However, the efficiency of fork blockage by Tus-Ter does not exceed 50% in vivo despite its apparent ability to almost permanently arrest replication forks in vitro. Here we use data from single-molecule DNA replication assays and structural studies to show that both polarity and fork-arrest efficiency are determined by a competition between rates of Tus displacement and rearrangement of Tus-Ter interactions that leads to blockage of slower moving replisomes by two distinct mechanisms. To our knowledge this is the first example where intrinsic differences in rates of individual replisomes have different biological outcomes.

Resolution of the Holliday junction recombination intermediate by human GEN1 at the single-molecule level.

Human GEN1 is a cytosolic homologous recombination protein that resolves persisting four-way Holliday junctions (HJ) after the dissolution of the nuclear membrane. GEN1 dimerization has been suggested to play key role in the resolution of the HJ, but the kinetic details of its reaction remained elusive. Here, single-molecule FRET shows how human GEN1 binds the HJ and always ensures its resolution within the lifetime of the GEN1-HJ complex. GEN1 monomer generally follows the isomer bias of the HJ in its initial binding and subsequently distorts it for catalysis. GEN1 monomer remains tightly bound with no apparent dissociation until GEN1 dimer is formed and the HJ is fully resolved. Fast on- and slow off-rates of GEN1 dimer and its increased affinity to the singly-cleaved HJ enforce the forward reaction. Furthermore, GEN1 monomer binds singly-cleaved HJ tighter than intact HJ providing a fail-safe mechanism if GEN1 dimer or one of its monomers dissociates after the first cleavage. The tight binding of GEN1 monomer to intact- and singly-cleaved HJ empowers it as the last resort to process HJs that escape the primary mechanisms.

Single-strand repair of EWAS 1 lesion of triangular fibrocartilage complex.

PURPOSE: To report the results of our modified technique for repair of the EWAS 1 lesion of triangular fibrocartilage complex (TFCC). METHODS: This retrospective case series reviewed 22 consecutive patients with EWAS 1 TFCC tear. Arthroscopic repair was done using our modified double-loop arthroscopic outside-in technique which is originally described by Mathoulin and Del Piñal. The repair was performed using single-strand suture and 18-gauge cannula, having three passes through the tear. Follow-ups ranged from 24 to 33 months with an average of 29.3 months. The results were evaluated by the Modified Mayo Wrist Score (MMWS), Visual Analog Score (VAS). In addition, range of motion (ROM) and power grip were compared with the contralateral side. RESULTS: The mean age was 23 years. The dominant side was affected in 16 wrists. There was postoperative improvement of the all functional outcome measures (MMWS, VAS, ROM, and power grip). All the patients returned to their previous activities with no reported intra- or postoperative complications. CONCLUSIONS: The described outside-in technique is safe and effective technique for repair of EWAS 1 TFCC tear. LEVEL OF EVIDENCE: Therapeutic, case series, level IV.

Missed cleavage opportunities by FEN1 lead to Okazaki fragment maturation via the long-flap pathway.

RNA-DNA hybrid primers synthesized by low fidelity DNA polymerase α to initiate eukaryotic lagging strand synthesis must be removed efficiently during Okazaki fragment (OF) maturation to complete DNA replication. In this process, each OF primer is displaced and the resulting 5'-single-stranded flap is cleaved by structure-specific 5'-nucleases, mainly Flap Endonuclease 1 (FEN1), to generate a ligatable nick. At least two models have been proposed to describe primer removal, namely short- and long-flap pathways that involve FEN1 or FEN1 along with Replication Protein A (RPA) and Dna2 helicase/nuclease, respectively. We addressed the question of pathway choice by studying the kinetic mechanism of FEN1 action on short- and long-flap DNA substrates. Using single molecule FRET and rapid quench-flow bulk cleavage assays, we showed that unlike short-flap substrates, which are bound, bent and cleaved within the first encounter between FEN1 and DNA, long-flap substrates can escape cleavage even after DNA binding and bending. Notably, FEN1 can access both substrates in the presence of RPA, but bending and cleavage of long-flap DNA is specifically inhibited. We propose that FEN1 attempts to process both short and long flaps, but occasional missed cleavage of the latter allows RPA binding and triggers the long-flap OF maturation pathway.

Arthroscopic Bankart repair with remplissage versus Latarjet procedure for management of engaging Hill-Sachs lesions with subcritical glenoid bone loss in traumatic anterior shoulder instability: a systematic review and meta-analysis.

BACKGROUND: A large engaging Hill-Sachs lesion (HSL) with subcritical glenoid bone loss (GBL) is approached through either increasing the glenoid arc by the Latarjet procedure or converting the HSL to an extra-articular defect by arthroscopic Bankart repair with remplissage (BRR). Until now, there has been no evidence-based consensus about which of these 2 most appropriate procedures is the better surgical choice. The purpose of this study was to analyze the current literature comparing results of BRR vs. the Latarjet procedure in the treatment of engaging HSLs with subcritical GBL. METHODS: A comprehensive review of the PubMed and Cochrane databases was completed for studies that compared the clinical outcomes and complications of BRR vs. the Latarjet procedure with minimum follow-up of 2 years. The outcome measures analyzed included postoperative Rowe score, visual analog scale pain score, postoperative range of motion (ROM), and rates of recurrent instability and other complications. RESULTS: Overall, 4 articles (level III evidence in 3 and level II in 1) were included from an initial 804 abstracts. The study population consisted of a total of 379 patients, of whom 194 underwent BRR and 185 underwent the Latarjet procedure. There were no unacceptable differences in baseline characteristics between the 2 groups. For the rate of recurrent instability, both groups had comparable risk ratios (RRs) (N = 379; RR, 0.72; 95% confidence interval [CI], 0.37-1.41). The risk of other complications was significantly increased with the Latarjet procedure (by about 7 times) relative to the the BRR procedure (N = 379; RR, 7.37; 95% CI, 2-27). Both groups had comparable postoperative Rowe scores (n = 190; mean difference [MD], -0.9; 95% CI, -3.45 to 1.7) and visual analog scale pain scores (n = 347; MD, -0.2; 95% CI, -0.6 to 0.2). Moreover, both groups had comparable postoperative external rotation ROM (MD, -1.7°; 95% CI, -9.4° to 6°) and internal rotation ROM (MD, 1.95°; 95% CI, -5.35° to 9.25°). There was substantial heterogeneity in the effect of both procedures on postoperative pain and ROM (external rotation and internal rotation). CONCLUSION: Both the BRR and Latarjet procedures are effective for the management of engaging HSLs with subcritical GBL and give comparable clinical outcomes. However, given the fewer overall postoperative complications, remplissage may be safer. The results of the included studies were adequately consistent for most analyzed outcomes. However, for the intervention effect on postoperative pain and ROM, there was a small body of evidence, limiting the strength of the reported conclusions.

Dynamic structure mediates halophilic adaptation of a DNA polymerase from the deep-sea brines of the Red Sea.

The deep-sea brines of the Red Sea are remote and unexplored environments characterized by high temperatures, anoxic water, and elevated concentrations of salt and heavy metals. This environment provides a rare system to study the interplay between halophilic and thermophilic adaptation in biologic macromolecules. The present article reports the first DNA polymerase with halophilic and thermophilic features. Biochemical and structural analysis by Raman and circular dichroism spectroscopy showed that the charge distribution on the protein's surface mediates the structural balance between stability for thermal adaptation and flexibility for counteracting the salt-induced rigid and nonfunctional hydrophobic packing. Salt bridge interactions via increased negative and positive charges contribute to structural stability. Salt tolerance, conversely, is mediated by a dynamic structure that becomes more fixed and functional with increasing salt concentration. We propose that repulsive forces among excess negative charges, in addition to a high percentage of negatively charged random coils, mediate this structural dynamism. This knowledge enabled us to engineer a halophilic version of Thermococcus kodakarensis DNA polymerase.-Takahashi, M., Takahashi, E., Joudeh, L. I., Marini, M., Das, G., Elshenawy, M. M., Akal, A., Sakashita, K., Alam, I., Tehseen, M., Sobhy, M. A., Stingl, U., Merzaban, J. S., Di Fabrizio, E., Hamdan, S. M. Dynamic structure mediates halophilic adaptation of a DNA polymerase from the deep-sea brines of the Red Sea.

Editorial Commentary: Medial Patellofemoral Complex: Driving a Better Understanding of Medial Knee Anatomy.

Although its importance as the prime restraint to lateral patellar instability is undoubted, the anatomy of the medial patellofemoral ligament has never been agreed on. Since it was first described by Warren and Marshall in 1979, most of the anatomic studies confirmed its presence in 90% of the cases, but they usually provide inconsistent descriptions of its femoral and patellar attachments. It is proven that length changes in the reconstructed medial patellofemoral ligament depend principally on the femoral attachment site. Moreover, the femoral attachment site affects the patellar tilt, translation, and joint reaction force. Because of the early inconsistent descriptions of the medial patellofemoral ligament attachment sites, some authors have suggested that its anatomy is not fixed or may be patient specific.

Scarf versus long chevron osteotomies for the treatment of hallux valgus: A prospective randomized controlled study.

BACKGROUND: The aim of this study is to compare scarf osteotomy and long chevron osteotomy in treatment of hallux valgus deformity regarding operative time, power of correction and complications. DESIGN: A prospective randomized controlled comparative trial. METHODS: 48 cases with hallux valgus were divided randomly in 2 groups (21 treated by scarf and 22 treated by long chevron osteotomy and 5 were missed during follow up), average age 36 years, follow up time was average of 25.9 months. Patients were assessed clinically, radiologically, and functional scoring system of American College of Foot and ankle Surgeons (ACFAS)was used both pre and postoperatively. RESULTS: Operative time was 69min in scarf group compared to 63min to long chevron group, radiological correction showed no statistically significant difference between both groups while functional improvement in ACFAS score was in favour of long chevron group 69.1% compared to scarf group 57.5% CONCLUSIONS: Both osteotomies possess almost identical corrective power of the IMA (intermetatarsal angle) and similar clinical outcomes with slightly shorter operative time and subjective technical simplicity for the long chevron osteotomy.

Impact of ohmicsonication treatment on pectinmethylesterase in not-from-concentrate orange juice.

The present study investigates the application of ohmicsonication (OS) as a new hurdle technology for pasteurization of Not-from-concentrate orange juice (NFCOJ). OS process parameters to inactivate pectinmethylesterase (PME) activity in NFCOJ were optimized using response surface methodology. The influence of Sonication (S), Thermosonication (TS), Ohmic heating (OH) and OS on inactivation of PME were compared to conventional heat (CH) treatment. Their effects on physical, chemical and microbiological contents were included. In comparison to fresh orange juice, the inactivation of PME was 96%, 95%, 89%, 90% and 29% for OS, OH, TS, CH and S treatments, respectively. Highest cloud value was obtained for OS (1.240 A) treatment. OS treatment gave a lower vitamin C loss compared to TS, OH and CH treatments. A significant increase in the total phenolic content were obtained in the following order OS > TS > OH > CH. OS treated juice also contained the lowest value of hydroxymethyl furfural (0.90 mg/L) compared to OH (0.95 mg/L), TS (1.37 mg/L) and CH (2.72 mg/L) treated samples. Overall, the results indicated that OS can be integrated as a substitute to pasteurization of NFCOJ.

Risk of second malignancies among survivors of pediatric thyroid cancer.

BACKGROUND: Thyroid carcinoma is a very rare tumor in the pediatric age group, accounting for only 1.5-3% of childhood carcinomas in the United States and Europe. We aimed to identify the risk of a second malignancy among pediatric thyroid cancer survivors. METHODS: The cohort analysis consisted of pediatric cancer patients aged less than 20 years, diagnosed with a primary thyroid cancer, identified by site code ICD-0-3: C739, and reported to the SEER 9 database between 1973 and 2013. They were followed up until December 31, 2013; the end of the study period, or up to death if earlier. RESULTS: Out of 1769 patients diagnosed primarily with thyroid carcinoma, 42 patients had a total of 45 incidences of subsequent malignancies. The mean age of patients at the initial diagnosis of thyroid cancer was 16 years. Females (90.5%) had a significantly higher incidence of second malignancies (SM) than males (9.5%). The overall Standardized Incidence Ratio (SIR) of SM in the study patients was higher than expected (SIR = 1.48). Some specific sites showed significantly higher incidences: the salivary glands (SIR = 33.95), the gum and other parts of the mouth [excluding the lips, tongue, salivary glands and floor of the mouth] (SIR = 24.53)*** and the kidneys (SIR = 5.72). The overall risk of SM in patients who had received radioactive iodine was higher than expected (SIR = 4.41). The cumulative incidence of SM after treatment of thyroid cancer in children increases steadily over 40 years (11.92%). CONCLUSIONS: Race, gender, histological subtypes, and radioactive iodine are potentially significant prognostic factors for the development of SM among pediatric thyroid cancer survivors. Identification of underlying mechanisms that raise the risk of SM is important for both treatment and follow-up strategies.

Bioactive compounds and antioxidant activities of some cereal milling by-products.

The present study was performed to evaluate the phytochemicals profiles of some cereal milling by-products such as wheat (bran, germ and shorts), rice (bran, germ and husk) and corn (bran, germ and germ meal) to assess their potentiality as bioactive compounds sources. Distilled water, ethanol, methanol, and acetone separately were used as solvents for the extraction of phytochemicals compounds. The antioxidant activity (AOA), total phenolics content (TPC), and total flavonoids content (TFC) of the extracts were investigated using various in vitro assays. The results showed that tannins content was ranged from 113.4 to 389.5 (mg/100 g sample).The study revealed that TPC and TFC of cereal by-products extracts were significantly different for various solvents. TPC content varied from 366.1 to 1924.9 mg/100 g and TFC content varied from 139.3 to 681.6 mg/100 g. High carotenoids content was observed for corn germ meal and minimum for wheat bran. Distilled water, ethanol and methanol extracts showed significantly different antioxidant activity. Significant variations were observed with regard to AOA of different cereal by-products by using various solvents. The ethanol and methanol were observed to be the best solvents to extract phenolic compounds and antioxidant activity, while acetone extract showed less efficiency. Also, the cereal milling by-products were rich in bioactive compounds and could be used as a value added products.