Efficacy and tolerability of initial triple combination therapy with metformin, dapagliflozin and saxagliptin compared with stepwise add-on therapy in drug-naïve patients with type 2 diabetes (TRIPLE-AXEL study): A multicentre, randomized, 104-week, open-label, active-controlled trial.

AIM: To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add-on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D). MATERIALS AND METHODS: This multicentre, randomized, 104-week, open-label trial randomized 105 patients with drug-naïve T2D (with HbA1c level ≥ 8.0%, < 11.0%) to the TCT (1000 mg of metformin, 10 mg of dapagliflozin and 5 mg of saxagliptin once daily) or SAT (initiated with metformin, followed by glimepiride and sitagliptin) groups. The primary outcome was the proportion of patients who achieved an HbA1c level of less than 6.5% without hypoglycaemia, weight gain of 5% or higher, or discontinuation of drugs because of adverse events at week 104. RESULTS: HbA1c reduction from baseline at week 104 was similar between the groups (the least squares mean change was -2.56% in the TCT group vs. -2.75% in the SAT group). The primary outcome was achieved in 39.0% and 17.1% of the TCT and SAT groups, respectively, with a risk difference of 22.0 (95% confidence interval 3.0, 40.8; P = .027). HbA1c level less than 6.5% at week 104 was 46.3% in both the TCT and SAT groups, whereas the incidence of hypoglycaemia, weight gain, or discontinuation of drugs was 16.7% and 62.0% in the TCT and SAT groups, respectively (P < .001). TCT was well-tolerated and had fewer adverse events than SAT. CONCLUSIONS: Among newly diagnosed patients with T2D, initial TCT effectively lowered HbA1c levels with higher tolerability and safety than SAT for 104 weeks, suggesting a novel strategy for initial combination therapy in T2D patients.

Dual add-on therapy of gemigliptin and dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin alone: The SOLUTION 2 study.

AIM: To evaluate the efficacy and safety of gemigliptin and dapagliflozin dual add-on therapy (GEMI + DAPA) to metformin in type 2 diabetes (T2D) patients who had inadequate glycaemic control on metformin alone, compared with a single add-on of either gemigliptin (GEMI) or dapagliflozin (DAPA) to metformin. MATERIALS AND METHODS: In this randomized, double-blind, double-dummy, active-controlled, parallel-group, phase 3 study, 469 T2D patients treated with a stable dose of metformin for 8 weeks or longer were randomized to receive GEMI + DAPA (n = 157) and either GEMI (n = 156) or DAPA (n = 156). The primary endpoint was change in HbA1c levels from baseline at week 24. RESULTS: Baseline characteristics including body mass index and T2D duration were similar among groups. At week 24, the least square mean changes in HbA1c from baseline were -1.34% with GEMI + DAPA, -0.90% with GEMI (difference between GEMI + DAPA vs. GEMI -0.44% [95% confidence interval {CI}: -0.58% to -0.31%], P < .01) and -0.78% with DAPA (difference between GEMI + DAPA vs. DAPA -0.56% [95% CI: -0.69% to -0.42%], P < .01). Both upper CIs were less than 0, demonstrating the superiority of GEMI + DAPA for lowering HbA1c. The rates of responders achieving HbA1c less than 7% and less than 6.5% were greater with GEMI + DAPA (84.9%, 56.6%) than with GEMI (55.3%, 32.2%) and DAPA (49.3%, 15.3%). The incidence rate of adverse events was similar across groups, with low incidence rates of hypoglycaemia, urinary tract infection and genital infection. CONCLUSIONS: These results suggest that the addition of GEMI + DAPA to metformin as triple combination therapy was effective, safe and well-tolerated, especially for T2D patients who experienced poor glycaemic control on metformin alone.

Effects of dapagliflozin compared with glimepiride on body composition in Asian patients with type 2 diabetes inadequately controlled with metformin: The BEYOND study.

AIMS: To evaluate the effect of dapagliflozin on body composition such as total body fat (BF) mass, abdominal visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) areas compared with glimepiride in Korean patients with type 2 diabetes. MATERIALS AND METHODS: This was a 52-week, multicentre, randomized, parallel-group, open-label, Phase IV (NCT02564926) study. Patients with inadequate glycaemic control (glycated haemoglobin ≥7.0% and <10.0%) on metformin monotherapy (≥1000 mg/day) were randomized 1:1 to receive dapagliflozin 10 mg/day or glimepiride 1-2 mg/day for 12 months as an add-on to metformin. Baseline and end of study body composition evaluations included dual-energy X-ray absorptiometry and abdominal computed tomography scans. RESULTS: Of 124 enrolled patients from 14 centres, 121 received study treatment (dapagliflozin: 60; glimepiride: 61) and 106 (85.5%) completed the study. Over 52 weeks, the dapagliflozin group showed the following differences versus the glimepiride group: -2.59 kg BF mass, -1.94% BF%, -17.55 cm2 VAT area, -18.39 cm2 SAT area, -0.46% glycated haemoglobin, -18.25 mg/dl fasting blood glucose, -3.7 kg weight, -2.21 cm waist circumference, -1.37 kg/m2 body mass index, -6.81 mmHg systolic blood pressure and +657.71 ng/ml in adiponectin; all were statistically significant. Both groups had similar incidences of adverse events; however, hypoglycaemic events were mainly (12 of 15) reported in the glimepiride group. CONCLUSION: Dapagliflozin reduced total BF mass, abdominal VAT and SAT areas, and showed better glycaemic control than glimepiride. Being safe and well-tolerated, dapagliflozin appears to be a more favourable alternative to sulphonylureas as add-on therapy after metformin monotherapy failure in Korean patients with type 2 diabetes.

One-Pot Synthesis of Unprotected 2-Acylpyrroles from 1,2,3-Triazoles and 2-Hydroxymethylallyl Carbonates.

An efficient, tandem one-pot approach to synthesize multisubstituted 2-acylpyrroles from readily prepared N-tosyl triazoles and 2-hydroxymethylallyl carbonates is reported. The reaction proceeds via Rh(II)-catalyzed O-H insertion, [3,3]-sigmatropic rearrangement, Pd(0)-catalyzed oxidative addition, intramolecular cyclization, DBU-promoted E1cB elimination, double bond isomerization, and aromatization, enabling the disconnection and formation of multiple bonds in one reactor. The approach represents a highly regioselective way to access di-, tri-, and tetra-substituted NH pyrroles with high efficiency.

Pd-catalyzed oxa-[4 + n] dipolar cycloaddition using 1,4-O/C dipole synthons for the synthesis of O-heterocycles.

Transition metal-catalyzed dipolar cycloaddition is one of the most efficient and powerful synthetic strategies to produce diverse heterocycles. In particular, for the construction of oxygen-containing heterocycles, which are valuable structural motifs found in pharmaceuticals and natural compounds, transition metal-catalyzed oxa-dipolar cycloaddition using an oxygen-containing dipole has emerged as a promising method. In recent years, the 1,4-O/C dipole synthons 2-alkylidenetrimethylene carbonate and 2-hydroxymethylallyl carbonate have been developed and successfully applied to palladium-catalyzed oxa-[4 + n] dipolar cycloadditions with diverse dipolarophiles. In this review, we summarize recent advances in palladium-catalyzed oxa-[4 + n] dipolar cycloadditions using 1,4-O/C dipoles including asymmetric catalysis and divergent catalysis toward five- to nine-membered O-heterocycles.

Towards an integrative hope-dysfunctional beliefs perspective to personal recovery in schizophrenia: a path analysis.

BACKGROUND: Evidence shows that negative symptoms of schizophrenia and underlying dysfunctional cognition are related to persistently low functioning and quality of life. However, despite the abundance of existing recovery programs for people with schizophrenia, few have examined whether and how the widely-adopted hope-motivation recovery pathway and the deficit-oriented cognitive pathway might converge to influence functioning and quality of life. METHODS: A cross-sectional, quantative survey recruited a convenient sample of adult outpatients with DSM-5 schizophrenia spectrum disorders and low social functioning (n = 124). Self-reported measurements included personal recovery (30-item Mental Health Recovery Measure), social functioning (8-item Social Functioning Questionnaire), hope (12-item Hope Scale), quality of life (28-item World Health Organization Quality of Life Scale-Abbreviated Version-Hong Kong), defeatist beliefs (15-item extracted from Dysfunctional Attitude Scale), and asocial beliefs (15-item extracted from Revised Social Anhedonia Scale). Correlation analysis and structural equation modelling was applied to investigate how the two pathways intertwined to predict social functioning and quality of life. RESULTS: Asocial beliefs and hope separately mediated two partial mediation pathways from defeatist beliefs to recovery outcomes (social functioning and personal recovery). Meanwhile, defeatist beliefs, social functioning, and personal recovery further predicted quality of life. CONCLUSIONS: This is one of the very few studies that provides empirical evidence of a deficit-strength linkage in the recovery from schizophrenia. Remediation of dysfunctional beliefs and the injection of hope and successful experiences should be undertaken concurrently in recovery as they are associated with differential effects on enhancing social functioning and personal recovery, which then converge and contribute to a better quality of life.

Medial Meniscus Posterior Root Repair Restores Contact Pressure and Contact Area to Its Native State Even After Opening-Wedge High Tibial Osteotomy: A Cadaveric Biomechanical Study.

PURPOSE: To elucidate the effect of medial meniscus posterior root (MMPR) repair during opening-wedge high tibial osteotomy (OWHTO) in terms of contact pressure (CP) and contact area (CA). METHODS: Nine fresh-frozen human cadaveric knee specimens were included. Each specimen was tested under 9 conditions comprising 3 different degrees of correction during OWHTO (neutral, 5° of valgus, and 10° of valgus) and 3 different types of MMPR conditions (intact, torn, and repaired). The prepared specimens were attached to a customized tibiofemoral jig in a fully extended state. The CP and CA generated by a tibiofemoral axial load of 650 N was recorded using the Tekscan sensor's pressure mapping software. Statistical analysis was performed using a repeated measures analysis of variance. RESULTS: The increased CP and decreased CA in torn MMPR was decreased and increased, respectively, to the intact MMPR after repairing, irrespective of whether OWHTO was performed. The mean CP at a correction angle of 5° of valgus was 0.4067 ± 0.0768 MPa for intact MMPR, which increased to 0.7340 ± 0.1593 MPa for the torn MMPR and decreased to 0.3614 ± 0.0639 MPa for the repaired MMPR. In addition, the proportion of decrease in CP and increase in CA after MMPR repair was constant, compared with the torn MMPR, irrespective of the degree of correction during OWHTO. CONCLUSIONS: MMPR repair decreases CP and increases CA, irrespective of whether OWHTO is performed. The biomechanical advantage of repairing torn MMPR is maintained, regardless of the degree of correction during OWHTO. CLINICAL RELEVANCE: Both OWHTO and MMPR repair are known to protect the medial compartment of the knee. However, there are concerns in performing 2 procedures simultaneously. Results of our study showed that concurrent repair of the MMPR during OWHTO is useful for protecting the medial compartment of the knee with respect to tibiofemoral contact biomechanics.

A Miniaturized Tri-Band Implantable Antenna for ISM/WMTS/Lower UWB/Wi-Fi Frequencies.

This study aims to design a compact antenna structure suitable for implantable devices, with a broad frequency range covering various bands such as the Industrial Scientific and Medical band (868-868.6 MHz, 902-928 MHz, 5.725-5.875 GHz), the Wireless Medical Telemetry Service (WMTS) band, a subset of the unlicensed 3.5-4.5 GHz ultra-wideband (UWB) that is free of interference, and various Wi-Fi spectra (3.6 GHz, 4.9 GHz, 5 GHz, 5.9 GHz, 6 GHz). The antenna supports both low and high frequencies for efficient data transfer and is compatible with various communication technologies. The antenna features an asynchronous-meandered radiator, a parasitic patch, and an open-ended square ring-shaped ground plane. The antenna is deployed deep inside the muscle layer of a rectangular phantom below the skin and fat layer at a depth of 7 mm for numerical simulation. Furthermore, the antenna is deployed in a cylindrical phantom and bent to check the suitability for different organs. A prototype of the antenna is created, and its reflection coefficient and radiation patterns are measured in fresh pork tissue. The proposed antenna is considered a suitable candidate for implantable technology compared to other designs reported in the literature. It can be observed that the proposed antenna in this study has the smallest volume (75 mm3) and widest bandwidth (181.8% for 0.86 GHz, 9.58% for 1.43 GHz, and 285.7% for the UWB subset and Wi-Fi). It also has the highest gain (-26 dBi for ISM, -14 dBi for WMTS, and -14.2 dBi for UWB subset and Wi-Fi) compared to other antennas in the literature. In addition, the SAR values for the proposed antenna are well below the safety limits prescribed by IEEE Std C95.1-1999, with SAR values of 0.409 W/Kg for 0.8 GHz, 0.534 W/Kg for 1.43 GHz, 0.529 W/Kg for 3.5 GHz, and 0.665 W/Kg for 5.5 GHz when the applied input power is 10 mW. Overall, the proposed antenna in this study demonstrates superior performance compared to existing tri-band implantable antennas in terms of size, bandwidth, gain, and SAR values.

Whole-genome sequencing and genetic characteristics of representative porcine reproductive and respiratory syndrome virus (PRRSV) isolates in Korea.

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is a macrophage-tropic arterivirus with extremely high genetic and pathogenic heterogeneity that causes significant economic losses in the swine industry worldwide. PRRSV can be divided into two species [PRRSV1 (European) and PRRSV2 (North American)] and is usually diagnosed and genetically differentiated into several lineages based on the ORF5 gene, which constitutes only 5% of the whole genome. This study was conducted to achieve nonselective amplification and whole-genome sequencing (WGS) based on a simplified sequence-independent, single-primer amplification (SISPA) technique with next-generation sequencing (NGS), and to genetically characterize Korean PRRSV field isolates at the whole genome level. METHODS: The SISPA-NGS method coupled with a bioinformatics pipeline was utilized to retrieve full length PRRSV genomes of 19 representative Korean PRRSV strains by de novo assembly. Phylogenetic analysis, analysis of the insertion and deletion (INDEL) pattern of nonstructural protein 2 (NSP2), and recombination analysis were conducted. RESULTS: Nineteen complete PRRSV genomes were obtained with a high depth of coverage by the SISPA-NGS method. Korean PRRSV1 belonged to the Korean-specific subtype 1A and vaccine-related subtype 1C lineages, showing no evidence of recombination and divergent genetic heterogeneity with conserved NSP2 deletion patterns. Among Korean PRRSV2 isolates, modified live vaccine (MLV)-related lineage 5 viruses, lineage 1 viruses, and nation-specific Korean lineages (KOR A, B and C) could be identified. The NSP2 deletion pattern of the Korean lineages was consistent with that of the MN-184 strain (lineage 1), which indicates the common ancestor and independent evolution of Korean lineages. Multiple recombination signals were detected from Korean-lineage strains isolated in the 2010s, suggesting natural interlineage recombination between circulating KOR C and MLV strains. Interestingly, the Korean strain GGYC45 was identified as a recombinant KOR C and MLV strain harboring the KOR B ORF5 gene and might be the ancestor of currently circulating KOR B strains. Additionally, two novel lineage 1 recombinants of NADC30-like and NADC34-like viruses were detected. CONCLUSION: Genome-wide analysis of Korean PRRSV isolates retrieved by the SISPA-NGS method and de novo assembly, revealed complex evolution and recombination in the field. Therefore, continuous surveillance of PRRSV at the whole genome level should be conducted, and new vaccine strategies for more efficient control of the virus are needed.

Rh(II)-Catalyzed C-N Bond Formation Using Enynones and N-H Imines: An Approach to Diarylmethylamines.

A Rh(II)-catalyzed furyl carbene N-H insertion reaction involving an N-sp2-hybridized imine is described, which represents an atom-economical route by which to access diarylmethylamine derivatives with high efficiency and broad substrate scope. An unusual reaction mechanism is proposed, in which the rhodium catalyst plays a dual role in facilitating enynone cyclization via activation and enhancement of the nucleophilicity of the NH imine.

Molecular characterization and antimicrobial susceptibility of Corynebacterium pseudotuberculosis isolated from skin abscesses of native Korean goats (Capra hircus coreanae).

AIMS: This study aimed to investigate the molecular characterization and antimicrobial susceptibility of Corynebacterium pseudotuberculosis from skin abscesses of Korean native black goats (KNBG, Capra hircus coreanae) in South Korea. METHODS AND RESULTS: A total of 83 isolates were recovered from skin abscesses of KNBG. Of these isolates, 74 isolates were identified as C. pseudotuberculosis by phospholipase D (PLD) gene-based PCR assay. Each of the isolates possessed all 18 virulence genes (FagA, FagB, FagC, FagD, SigE, SpaC, SodC, PknG, NanH, OppA, OppB, OppC, OppD, OppF, CopC, NrdH and CpaE). The genetic diversity of C. pseudotuberculosis isolates was assessed by the phylogenetic analysis using the concatenated sequences (3073 bp) of five housekeeping genes (fusA, dnaK, infB, groeL1 and leuA) for investigating their genetic diversity. In the results, the isolates belonged to three groups: group 1 (67 isolates), group 2 (one isolate) and group 3 (six isolates) within biovar ovis. However, the groups exhibited low genetic diversity (0.20%-0.41%). In the antimicrobial susceptibility test, most isolates were susceptible to tetracycline, vancomycin, chloramphenicol, ciprofloxacin, erythromycin, enrofloxacin, cefoxitin, ampicillin, gentamycin, cephalothin and doxycycline, whereas they were not susceptible to cefotaxime, trimethoprim and streptomycin. CONCLUSION: This results suggest the involvement of relatively few clones of C. pseudotuberculosis in Korea. Further, present isolates can threaten public health due to potentially virulent strains with all 18 virulence genes and non-susceptible strains to clinically important antibiotics (CIA) and highly important antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to investigate the genetic diversity and potential pathogenicity of C. pseudotuberculosis biovar ovis isolates from skin abscesses of KBNG in South Korea, and could provide useful information in controlling its infections.

Kinematically aligned total knee arthroplasty restores more native medial collateral ligament strain than mechanically aligned total knee arthroplasty.

PURPOSE: Kinematically aligned total knee arthroplasty (KA TKA) targets restoration of patient-specific alignment and soft tissue laxity. However, whether KA TKA reproduces native soft tissue strain remains unclear. This cadaveric study tested the hypothesis that KA TKA would better restore the quantitative strain and strain distribution of medial collateral ligament (MCL) to the native healthy knee compared to mechanically aligned (MA) TKA. METHODS: Twenty-four fresh-frozen cadaver knees (12 pairs) were mounted on a customized knee squatting simulator to measure MCL strain during flexion. For each pair, one knee was assigned to KA TKA and the other to MA TKA. During KA TKA, the amount of femur and tibia resected was equivalent to implant thickness without MCL release using the calipered measuring technique. MA TKA was performed using conventional measured resection techniques. MCL strain was measured using a video extensometer (Mercury® RT RealTime tracking system, Sobriety s.r.o, Czech Republic). MCL strain and strain distribution during knee flexion were measured, and the measurements compared between native and post-TKA conditions. RESULTS: Mean and peak MCL strain were similar between KA TKA and native knees at all flexion angles (p > 0.1 at all flexion angles) while mean strain at all flexion angles and peak strain at ≥ 60º of MA TKA were approximately twice those of the native knees (p < 0.05 at ≥ 60º of flexion). In addition, greater MCL strain was observed in 4 of 12 regions of interest (ROI) after MA TKA (M1, M2, P1 and P2) compared to the native knee, whereas after KA TKA, MCL strain measurements were similar at all but 1 ROI (P2). CONCLUSIONS: KA TKA restored a more native amount and distribution of MCL strain compared to MA TKA. These findings provide clues for understanding why patients may experience better performance and more normal knee sensations after KA TKA compared to MA TKA. LEVEL OF EVIDENCE: Therapeutic study, Level I.

Guided-Motion Bicruciate-Stabilized Total Knee Arthroplasty Reproduces Native Medial Collateral Ligament Strain.

Background and Objectives: Guided-motion bicruciate-stabilized (BCS) total knee arthroplasty (TKA) includes a dual cam-post mechanism with an asymmetric bearing geometry that promotes normal knee kinematics and enhances anterior-posterior stability. However, it is unclear whether the improved biomechanics after guided-motion BCS TKA reproduce soft tissue strain similar to the strain generated by native knees. The purpose of this cadaveric study was to compare medial collateral ligament (MCL) strain between native and guided-motion BCS TKA knees using a video extensometer. Materials and Methods: Eight cadaver knees were mounted onto a customized knee squatting simulator to measure MCL strain during flexion in both native and guided-motion BCS TKA knees (Journey II-BCS; Smith & Nephew, Memphis, TN, USA). MCL strain was measured using a video extensometer (Mercury® RT RealTime tracking system, Sobriety s.r.o, Kurim, Czech Republic). MCL strain level and strain distribution during knee flexion were compared between the native and guided-motion BCS TKA conditions. Results: The mean and peak MCL strain were similar between native and guided-motion BCS TKA knees at all flexion angles (p > 0.1). MCL strain distribution was similar between native and BCS TKA knees at 8 of 9 regions of interest (ROIs), while higher MCL strain was observed after BCS TKA than in the native knee at 1 ROI in the mid portion of the MCL at early flexion angles (p < 0.05 at ≤30° of flexion). Conclusions: Guided-motion BCS TKA restored the amount and distribution of MCL strain to the values observed on native knees.

Host-Specific Restriction of Avian Influenza Virus Caused by Differential Dynamics of ANP32 Family Members.

BACKGROUND: Influenza viruses must utilize host factors to complete their lifecycle. Species-specific differences in host factors between birds and mammals mean that avian influenza viruses (AIVs) replicate well in avian hosts but not in human hosts. Acidic nuclear phosphoprotein 32 family member A (ANP32A) has been identified as the host restriction factor for the viral polymerase (vPol) activity of AIVs. The ANP32A belongs to the conserved ANP32 family, the functional roles of which during viral replication remain unclear. METHODS: In this study, we targeted chicken ANP32A using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome editing to examine the functional roles of ANP32A and other members of the ANP32 family. RESULTS: We showed that chicken ANP32A only, not ANP32B and ANP32E, plays a pivotal role in supporting vPol activity of AIVs. Furthermore, we found that the human ANP32C, ANP32D, and ANP32E have suppressive effects on vPol activity in contrast to human ANP32A and ANP32B. CONCLUSIONS: Chicken and human ANP32 family members had different effects on vPol activity, suggesting that species-specific vPol activity of AIVs could be caused by the differential functions and overall competency of ANP32 family members.

Pre-screening of patient-reported symptoms using the Edmonton Symptom Assessment System in outpatient palliative cancer care.

OBJECTIVES: Although early palliative care is associated with a better quality of life and improved outcomes in end-of-life cancer care, the criteria of palliative care referral are still elusive. METHODS: We collected patient-reported symptoms using the Edmonton Symptom Assessment System (ESAS) at the baseline, first and second follow-up visits. A total of 71 patients were evaluable, with a median age of 65 years, male (62%) and Eastern Cooperative Oncology Group (ECOG) performance status distribution of 1/2/3 (28%/39%/33%) respectively. RESULTS: Twenty (28%) patients had moderate/severe symptom burden with the mean ESAS ≥ 5. Interestingly, most of the patients with moderate/severe symptom burdens (ESAS ≥ 5) had globally elevated symptom expression. While the mean ESAS score was maintained in patients with mild symptom burden (ESAS < 5; 2.7 at the baseline; 3.4 at the first follow-up; 3.0 at the second follow-up; p = .117), there was significant symptom improvement in patients with moderate/severe symptom burden (ESAS ≥ 5; 6.5 at the baseline; 4.5 at the first follow-up; 3.6 at the second follow-up; p < .001). CONCLUSIONS: In conclusion, advanced cancer patients with ESAS ≥ 5 may benefit from outpatient palliative cancer care. Pre-screening of patient-reported symptoms using ESAS can be useful for identifying unmet palliative care needs in advanced cancer patients.

Technical variation of trans-articular sacroiliac joint (SIJ) fusion using three screws considering the effects of sacral dysplasia in patients with non-traumatic SIJ pain.

BACKGROUND: This study evaluated the technical adequacy of trans-articular sacroiliac joint (SIJ) fusion using three screws for non-traumatic SIJ pain, considering different grades of sacral dysplasia. METHODS: Cadaveric CT data of unilateral sacropelvic complexes for 72 individuals (53.4 ± 8.4 years) were selected. A 3D model was reformatted into the plain lateral radiograph to mark the articular surface of the SIJ. Subjects were classified into dysplastic (DYS) and non-dysplastic sacrum (NDS) groups. Proximal (PS), middle (MS), and distal screws (DS) with 10-mm diameter were virtually introduced to the iliac bone and the SIJ on the lateral image with a 5-mm safety margin. On a corresponding axial image, each screw was advanced vertically to the sagittal plane with the same safety margin. The entry points for each screw to the endplate of S1 (S2) and to the corresponding anterior sacral margin on the lateral image were measured, along with the maximal screw lengths on the axial image. Whether each screw passed through the SIJ was determined. Different types of sacral dysplasia and screws were compared statistically. RESULTS: Thirty-eight (26.4%) cases were DYS, and 106 (73.6%) were NDS. The entry points of all screws were significantly more distal in DYS than in NDS groups. The PS and MS screw lengths differed significantly between the 2 groups. Incidences of short sacral fixation (< 10 mm) were significantly higher for the DS in both NDS (38.7%) and DYS (39.5%) groups. Incidences of screw pass were lowest for the MS in both NDS (43.4%) and DYS (47.4%) groups. CONCLUSIONS: Sacral dysplasia locates the SIJ more distally and therefore affects the entry point locations and screw lengths for all screws in trans-articular SIJ fusion, compared with a non-dysplastic sacrum. Moreover, three-screw fixation risks the development of unstable DS fixation and a high extra-articular fixation rate in MS.

Biological Oscillators in Nanonetworks-Opportunities and Challenges.

One of the major issues in molecular communication-based nanonetworks is the provision and maintenance of a common time knowledge. To stay true to the definition of molecular communication, biological oscillators are the potential solutions to achieve that goal as they generate oscillations through periodic fluctuations in the concentrations of molecules. Through the lens of a communication systems engineer, the scope of this survey is to explicitly classify, for the first time, existing biological oscillators based on whether they are found in nature or not, to discuss, in a tutorial fashion, the main principles that govern the oscillations in each oscillator, and to analyze oscillator parameters that are most relevant to communication engineer researchers. In addition, the survey highlights and addresses the key open research issues pertaining to several physical aspects of the oscillators and the adoption and implementation of the oscillators to nanonetworks. Moreover, key research directions are discussed.

UCMAC: A Cooperative MAC Protocol for Underwater Wireless Sensor Networks.

This paper proposes a cooperative medium access control (MAC) protocol for underwater wireless sensor networks (UWSNs) named UCMAC, which fundamentally benefits from cooperative communication. In UCMAC, a source identifies cooperators and provides its destination with a list of the cooperators while also delineating their proximity to the destination. For erroneous reception of data packets, the destination then requests retransmission to the cooperators in a closest-one-first manner. A designated cooperator transmits the buffered data packet it has successfully overheard from the source or other cooperators. A signaling procedure and the various waiting times of the nodes are carefully designed to address the overheads that stem from cooperation. Through computer simulation, this paper evaluates UCMAC in terms of system throughput, latency, single-hop packet delivery ratio (PDR), and energy efficiency. The results show that UCMAC performs better than existing schemes, including MACA-U and CD-MACA.

Efficacy of Yeast' Vacuoles as Antimicrobial Agents to Escherichia coli Bacteremia in Rat.

Yeast vacuoles, lysosomes, are cell organelles that have antimicrobial activity against several bacteria in vitro. Lysosomes have a potential application to the treatment of pathogens such as antibiotics in vivo. Therefore, the in vivo efficacy of lysosomes was examined in a rat infection model against pathogenic Escherichia coli with varying susceptibilities to standard antimicrobial agents. Before in vivo testing, the concentration-dependent safety of lysosomes was confirmed by blood test and histopathology of normal rats. The therapeutic efficacy of lysosomes was examined in terms of the survival of E. coli in infected rat blood. The complete blood count and histopathology results were affected by the lysosomes concentration. In addition, the E. coli growth was inhibited by the initial injection of lysosomes. These results support the use of lysosomes as a bacterial inhibitor of an infected rat model.

A general approach to site-specific antibody drug conjugates.

Using an expanded genetic code, antibodies with site-specifically incorporated nonnative amino acids were produced in stable cell lines derived from a CHO cell line with titers over 1 g/L. Using anti-5T4 and anti-Her2 antibodies as model systems, site-specific antibody drug conjugates (NDCs) were produced, via oxime bond formation between ketones on the side chain of the incorporated nonnative amino acid and hydroxylamine functionalized monomethyl auristatin D with either protease-cleavable or noncleavable linkers. When noncleavable linkers were used, these conjugates were highly stable and displayed improved in vitro efficacy as well as in vivo efficacy and pharmacokinetic stability in rodent models relative to conventional antibody drug conjugates conjugated through either engineered surface-exposed or reduced interchain disulfide bond cysteine residues. The advantages of the oxime-bonded, site-specific NDCs were even more apparent when low-antigen-expressing (2+) target cell lines were used in the comparative studies. NDCs generated with protease-cleavable linkers demonstrated that the site of conjugation had a significant impact on the stability of these rationally designed prodrug linkers. In a single-dose rat toxicology study, a site-specific anti-Her2 NDC was well tolerated at dose levels up to 90 mg/kg. These experiments support the notion that chemically defined antibody conjugates can be synthesized in commercially relevant yields and can lead to antibody drug conjugates with improved properties relative to the heterogeneous conjugates formed by nonspecific chemical modification.