Zinc- and Fluoride-Releasing Bioactive Glass as a Novel Bone Substitute.

Bioglass 45S5, a silica-based glass, has pioneered a new field of biomaterials. Bioglass 45S5 promotes mineralization through calcium ion release and is widely used in the dental field, including toothpaste formulations. However, the use of Bioglass 45S5 for bone grafting is limited owing to the induction of inflammation, as well as reduced degradation and ion release. Phosphate-based glasses exhibit higher solubility and ion release than silica-based glass. Given that these glasses can be synthesized at low temperatures (approximately 1,000°C), they can easily be doped with various metal oxides to confer therapeutic properties. Herein, we fabricated zinc- and fluoride-doped phosphate-based glass (multicomponent phosphate [MP] bioactive glass) and further doped aluminum oxide into the MP glass (4% Al-MP glass) to overcome the striking solubility of phosphate-based glass. Increased amounts of zinc and fluoride ions were detected in water containing the MP glass. Doping of aluminum oxide into the MP glass suppressed the striking dissolution in water, with 4% Al-MP glass exhibiting the highest stability in water. Compared with Bioglass 45S5, 4% Al-MP glass in water had a notably reduced particle size, supporting the abundant ion release of 4% Al-MP glass. Compared with Bioglass 45S5, 4% Al-MP glass enhanced the osteogenesis of mouse bone marrow-derived mesenchymal stem cells. Mouse macrophages cultured with 4% Al-MP glass displayed enhanced induction of anti-inflammatory M2 macrophages and reduced proinflammatory M1 macrophages, indicating M2 polarization. Upon implanting 4% Al-MP glass or Bioglass 45S5 in a mouse calvarial defect, 4% Al-MP glass promoted significant bone regeneration when compared with Bioglass 45S5. Hence, we successfully fabricated zinc- and fluoride-releasing bioactive glasses with improved osteogenic and anti-inflammatory properties, which could serve as a promising biomaterial for bone regeneration.

Malpratice claims in cardiology and cardiac surgery: A medico-legal issue.

Medical liability has become a challenge in every physician's modern practice with the consequent loss of the physician's autonomy and an increase in "defensive medicine". From this perspective, the role of Legal Medicine in assessing medical liability has become increasingly specific and a homogenization of the methods of ascertainment is increasingly necessary, since such a process can contribute to strengthening the guarantees in professional liability procedures. Focusing on malpractice claims in the field of cardiology, the complexity of the management of cardiac pathologies and the frequency of severe adverse events implies the importance of a multi-disciplinary approach, together with the application of a shared ascertainment methodology. In particular, it is essential for the forensic pathologist to collaborate with experts in cardio-pathology, cardiology and/or cardiac surgery in cases of alleged medical liability in the cardiologic field and to follow the guidelines which have been produced to assist the expert dealing with deaths reflecting cardiac disease, in order to prevent criticism of case analysis in medico-legal environments and to promote the standardization of the structure of the juridical-legislative medical malpractice lawsuits.

A medico-legal definition of femicide.

Femicide refers to the extreme form of violence against someone belonging to the female gender, i.e. the killing of a woman. Research shows that, to date, gender-based violence remains largely a hidden phenomenon with prevalence often being underestimated by official statistics and data missing in numerous countries. It can be argued that the under-reporting may be suggestive of a legislative gap that needs addressing. This work aims to reach a shared medico-legal definition of femicide stemming from a comprehensive review of the current legislation of countries around the world. In addition, it appraises forensic pathology studies focusing on the murder of women as well as the most relevant documents published by prominent international organizations fighting violence against women. Review of the literature shows a scarcity of national legislations concerning specifically femicide, despite the attention given to this phenomenon by international organizations fighting violence against women. Additionally, a non-homogeneous framing of the term femicide arises from the forensic pathology literature and national laws. Starting from one of the funding principle of medical ethics - autonomy - authors propose to define femicide as a murder perpetrated because of a failure to recognize the victim's right to self-determination. This definition would give the forensic pathologist a central role in identifying femicide cases among the murders of women. A shared forensic approach is needed, ideally employing standardized methodology to compare international data and to standardize scientific research in the field.

Fabrication of Hydrogen Boride Thin Film by Ion Exchange in MgB2.

In this study, hydrogen boride films are fabricated by ion-exchange treatment on magnesium diboride (MgB2) films under ambient temperature and pressure. We prepared oriented MgB2 films on strontium titanate (SrTiO3) substrates using pulsed laser deposition (PLD). Subsequently, these films were treated with ion exchangers in acetonitrile solution. TOF-SIMS analysis evidenced that hydrogen species were introduced into the MgB2 films by using two types of ion exchangers: proton exchange resin and formic acid. According to the HAXPES analysis, negatively charged boron species were preserved in the films after the ion-exchange treatment. In addition, the FT-IR analysis suggested that B-H bonds were formed in the MgB2 films following the ion-exchange treatment. The ion-exchange treatment using formic acid was more efficient compared to the resin treatment; with respect to the amount of hydrogen species introduced into the MgB2 films. These ion-exchanged films exhibited photoinduced hydrogen release as observed in a powder sample. Based on the present study, we expect to be able to control the morphology and hydrogen content of hydrogen boride thin films by optimising the ion-exchange treatment process, which will be useful for further studies and device applications.

Incoherent transport across the strange-metal regime of overdoped cuprates.

Strange metals possess highly unconventional electrical properties, such as a linear-in-temperature resistivity1-6, an inverse Hall angle that varies as temperature squared7-9 and a linear-in-field magnetoresistance10-13. Identifying the origin of these collective anomalies has proved fundamentally challenging, even in materials such as the hole-doped cuprates that possess a simple bandstructure. The prevailing consensus is that strange metallicity in the cuprates is tied to a quantum critical point at a doping p* inside the superconducting dome14,15. Here we study the high-field in-plane magnetoresistance of two superconducting cuprate families at doping levels beyond p*. At all dopings, the magnetoresistance exhibits quadrature scaling and becomes linear at high values of the ratio of the field and the temperature, indicating that the strange-metal regime extends well beyond p*. Moreover, the magnitude of the magnetoresistance is found to be much larger than predicted by conventional theory and is insensitive to both impurity scattering and magnetic field orientation. These observations, coupled with analysis of the zero-field and Hall resistivities, suggest that despite having a single band, the cuprate strange-metal region hosts two charge sectors, one containing coherent quasiparticles, the other scale-invariant 'Planckian' dissipators.

Antibody-like proteins that capture and neutralize SARS-CoV-2.

To combat severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and any unknown emerging pathogens in the future, the development of a rapid and effective method to generate high-affinity antibodies or antibody-like proteins is of critical importance. We here report high-speed in vitro selection of multiple high-affinity antibody-like proteins against various targets including the SARS-CoV-2 spike protein. The sequences of monobodies against the SARS-CoV-2 spike protein were successfully procured within only 4 days. Furthermore, the obtained monobody efficiently captured SARS-CoV-2 particles from the nasal swab samples of patients and exhibited a high neutralizing activity against SARS-CoV-2 infection (half-maximal inhibitory concentration, 0.5 nanomolar). High-speed in vitro selection of antibody-like proteins is a promising method for rapid development of a detection method for, and of a neutralizing protein against, a virus responsible for an ongoing, and possibly a future, pandemic.

Effect of high ligation on survival of patients undergoing surgery for primary colorectal cancer and synchronous liver metastases.

BACKGROUND: Although R0 surgery is recommended for stage IV colorectal cancer, the degree of required lymphadenectomy has not been established. The aim of this study was to investigate the prognostic impact of high ligation (HL) of the feeding artery and the number of retrieved lymph nodes after R0 surgery for colorectal cancer and synchronous colorectal cancer liver metastasis (CRLM). METHODS: This was a multi-institutional retrospective analysis of patients with colorectal cancer and synchronous CRLM who had R0 surgery between January 1997 and December 2007. Clinical and pathological features were compared in patients who underwent HL and those who had a low ligation (LL). Kaplan-Meier analysis was performed to estimate the effect of HL on overall survival (OS). The impact of several risk factors on survival was analysed using the Cox proportional hazards model. RESULTS: Of 549 patients, 409 (74·5 per cent) had HL. Median follow-up was 51·4 months. HL significantly improved the 5-year OS rate (58·2 per cent versus 49·3 per cent for LL; P = 0·017). Multivariable analysis revealed HL to be a significant prognostic factor compared with LL (5-year mortality: hazard ratio (HR) 0·68, 95 per cent c.i. 0·51 to 0·90; P = 0·007). In subgroup analysis, the positive effect of HL on OS was greatest in patients with lymph node metastasis. CONCLUSION: HL of the feeding artery was associated with improved OS in patients with colorectal cancer and synchronous CRLM after R0 surgery.

ANTECEDENTES: Aunque se recomienda una cirugía R0 para el cáncer colorrectal (colorectal cancer, CRC) en estadio IV, no se ha establecido el grado de linfadenectomía requerida. El objetivo de este estudio fue investigar el impacto pronóstico de la ligadura alta (high ligation, HL) de la arteria que irriga el tumor y el número de ganglios linfáticos (lymph nodes, LN) identificados después de cirugía R0 en pacientes con cáncer colorrectal y metástasis hepáticas sincrónicas (colorectal cancer liver metastasis, CRLM). MÉTODOS: En este estudio se realizó un análisis retrospectivo multicéntrico de pacientes con CRC y CRLM sincrónicas en los que se realizó una cirugía R0 desde enero de 1997 hasta diciembre de 2007. Se compararon las características clínicas y patológicas entre los pacientes a los que, durante la cirugía R0, se practicó una HL frente a los que no se practicó esta técnica. El análisis de Kaplan-Meier se realizó para estimar el efecto de la HL en la supervivencia global (overall survival, OS). El impacto de varios factores de riesgo sobre la supervivencia se analizó utilizando el modelo de Cox de riesgo proporcional. RESULTADOS: Sobre un total de 549 pacientes, se realizó una HL en 409 (74,5%), y el período de seguimiento medio en esta cohorte fue de 51,4 meses. La HL mejoró significativamente la tasa de OS a los 5 años (HL 37,7% versus no HL 27,1%, P = 0,02). El análisis multivariable mostró que la HL era un factor pronóstico significativo en comparación con la no realización de una HL (cociente de riesgos instantáneos, hazard ratio, HR de muerte a 5 años = 0,68 (i.c. del 95% 0,51-0,90), P < 0,01)). En el análisis de subgrupos, el efecto positivo de la HL sobre la OS fue mayor en pacientes con metástasis ganglionares. CONCLUSIÓN: La ligadura alta de la arteria que irriga el tumor se asoció con una mejor OS en pacientes con CRC y CRLM sincrónicas después de una cirugía R0.

Breast cancer diagnosis based on lipid profiling by probe electrospray ionization mass spectrometry.

Probe electrospray ionization mass spectrometry (PESI-MS) is an ambient ionization-based mass spectrometry method that surpasses the original electrospray ionization technique in features such as the rapidity of analysis, simplicity of the equipment and procedure, and lower cost. This study found that the PESI-MS system with machine learning has the potential to establish a lipid-based diagnosis of breast cancer with higher accuracy, using a simpler approach. Rapid mass spectrometry for breast cancer.

Pyogenic spondylitis with acute course caused by Corynebacterium simulans.

Corynebacterium simulans was first reported in 2000. Although it is a member of the normal skin flora, some cases of C. simulans infection have been reported. Other Corynebacterium spp. rarely cause chronic pyogenic spondylitis, and pyogenic spondylitis caused by C. simulans has not been reported at all. Here we report a case of acute pyogenic spondylitis due to C. simulans. A 78-year-old man with diabetes mellitus visited our hospital with a 3-day history of lower back pain and fever. Blood culture revealed C. simulans and magnetic resonance images of lumbar vertebrae showed pyogenic spondylitis. He recovered after treatment by vancomycin for 9 weeks and was discharged home. No recurrence has been observed for half a year. This is likely the first reported case of pyogenic spondylitis by C. simulans. In general, Corynebacterium spp. cause chronic pyogenic spondylitis, but this case showed an acute course.

Efficacy of dimethyl fumarate in Japanese multiple sclerosis patients: interim analysis of randomized, double-blind APEX study and its open-label extension.

BACKGROUND: Current data for the use of dimethyl fumarate (DMF) in Japanese patients with relapsing-remitting multiple sclerosis (RRMS) is limited. OBJECTIVES: To assess the efficacy of DMF in Japanese patients with RRMS. METHODS: The phase 3, multinational APEX study (ClinicalTrials.gov identifier: NCT01838668) consisted of two parts: a 24-week double-blind part where subjects were randomized to receive DMF 240 mg or placebo twice daily in East Asian and Eastern European countries, and an open-label extension part where all subjects received DMF. The primary endpoint was the total number of new gadolinium-enhancing lesions in Weeks 12-24. In this interim analysis, we report efficacy data in the Japanese subgroup (DMF n = 56; placebo n = 58) over 72 weeks, including an extension phase. RESULTS: DMF reduced the total number of new gadolinium-enhancing lesions in Weeks 12-24 by 85% versus placebo (p < 0.0001). At Week 24, the annualized relapse rate was also reduced by 48% with DMF, versus placebo. DMF reduced the probability of relapse from Week 8 and was sustained. The number of gadolinium-enhancing lesions was maintained through 72 weeks. CONCLUSIONS: DMF demonstrated sustained efficacy in this Japanese subgroup. The results were consistent with those observed in studies of DMF enrolling primarily Caucasian patients.

Preferences for health information in middle-aged Japanese workers based on health literacy levels: a descriptive study.

OBJECTIVES: To describe the health information preferences in middle-aged Japanese workers based on health literacy (HL) levels and presence of medications. STUDY DESIGN: A cross-sectional study. METHODS: We performed a web-based questionnaire survey with Japanese workers aged below 60 years. HL was assessed using the total score of communicative skills (five items) and critical skills (four items) from the 14-item Health Literacy Scale. Regarding their health information preferences, participants were asked about the health information they wanted (four items), could easily understand (six items), or easily use (two items) and answered on a 4-point scale (strongly agree/agree/disagree/strongly disagree). The percentages of the affirmative responses (strongly agree or agree) were compared among tertiles based on the HL score. RESULTS: We obtained data from a total of 3387 volunteers, of whom 510 participants were on either antihypertensive, lipid-lowering, or antidiabetic drugs. Compared with the high HL and middle HL groups, low HL had fewer affirmative responses to most health information items. Health information items received 70% of affirmative responses even in the low HL level. They were visually shown by figures or pictures, highlighted by colors for important points, could be read in 1-2 min, and were accessed on the Internet, regardless of the presence of medications. Additionally, the explanation for mechanisms of medications or lifestyle to prevent or improve diseases showed high affinity in all HL levels, only for those on medications. CONCLUSIONS: This result generates a hypothesis that low HL individuals have a low interest in health information. Our data showed several possible forms of health information with high affinity based on HL levels that would help plan future population approaches.

Investigations on the Genus Rhizoecus (Hemiptera: Rhizoecidae) with Description of Two New Species from South America.

Neotropical species of the scale insect genus Rhizoecus Künckel d'Herculais (Hemiptera: Coccomorpha: Rhizoecidae) found in soil sample material of the Hungarian Natural History Museum were studied. Two new Rhizoecus species, Rhizoecus kontschani Kaydan and Konczné Benedicty sp. n., and Rhizoecus granaradewillinkae Kaydan and Szita sp. n., are described and illustrated based on the adult females. Also, the adult females of Rhizoecus keysensis Hambleton and Rhizoecus pseudocacticans Hambleton are illustrated. An identification key and new additional locality records for the currently known Rhizoecus species are provided.

Prognostic significance of genetic biomarkers in isocitrate dehydrogenase-wild-type lower-grade glioma: the need to further stratify this tumor entity - a meta-analysis.

The clinical outcomes of isocitrate dehydrogenase-wild-type (IDH-wt) lower-grade glioma (LGG) have been the subject of debate for some time. In this meta-analysis, we aimed to assess the prognostic values of several known genetic markers (e.g. TERT promoter mutation, H3F3A mutation, CDKN2A loss) in this tumor group. Four electronic databases, including PubMed, Scopus, Web of Science and Virtual Health Library, were searched for relevant articles. Pooled hazard ratio (HR) and corresponding 95% confidence interval (CI) for overall survival were calculated using a random-effect model weighted by an inverse variance method. A total of 11 studies were finally selected from 2274 articles for meta-analyses. Several genetic alterations were demonstrated to have a negative impact on prognosis of IDH-wt LGGs, specifically TERT promoter mutation (HR, 1.96; 95% CI, 1.42-2.70), H3F3A mutation (HR, 3.21; 95% CI, 1.86-5.55) and EGFR amplification (HR, 1.67; 95% CI, 1.02-2.74). However, CDKN loss, ATRX mutation and coexisting gain of chromosome 7/loss of chromosome 10 showed no clinical significance in this glioma entity. Our study results demonstrated that IDH-wt LGGs are heterogeneous in clinical outcome and not all tumors have a poor prognosis. The presence of TERT promoter mutation, H3F3A mutation and EGFR amplification showed negative prognostic impacts in this tumor entity. These genetic events can be used to better stratify patient outcomes.

Follow-up Survey of Donor Candidates for Living Related Kidney Transplantation With Prostate Cancer.

INTRODUCTION: With the increasing number of elderly kidney donor candidates due to the lack of available donors, prostate cancer has sometimes been detected in these candidates during pretransplant screening examinations. There are currently no guidelines or consensus on prostate cancer screening and treatment in donors. We retrospectively evaluated the clinical course of donor candidates with prostate cancer. METHODS: Between January 2006 and December 2016, 9 donor candidates for living related kidney transplantation were incidentally diagnosed with prostate cancer at our institution. All male kidney transplant donor candidates routinely received prostate-specific antigen (PSA) testing. The patients with PSA levels > 4.0 ng/mL underwent prostate biopsies. For future kidney transplantation, treatment for localized prostate cancer was prostatectomy. RESULTS: Seven low- or intermediate-risk patients according to the D'Amico risk classification underwent endoscopic prostatectomy, while 2 high-risk patients underwent high dose-rate brachytherapy to prioritize prostate cancer treatment. Of the 7 who underwent surgery, 3 patients ultimately became living related kidney transplantation donors for their wives. There was no recurrence of PSA elevation after treatment. CONCLUSION: This study showed that donor candidates with prostate cancer could safely donate a kidney after a thorough evaluation to exclude those with high-risk prostate cancer. Transmission of prostate cancer through kidney transplantation seems unlikely and robot-assisted laparoscopic prostatectomy may be feasible for donor candidates with localized prostate cancer.

Radical Prostatectomy for Localized Prostate Cancer in Renal Transplant Recipients: 13 Cases Studied at a Single Center.

OBJECTIVES: We aimed to evaluate the feasibility and efficacy of surgical prostatectomy in renal transplant recipients (RTRs). METHODS: Between January 2008 and February 2017, we identified 13 RTRs who were diagnosed with localized prostate cancer and underwent radical prostatectomy. We reviewed all available clinicopathologic data for these 13 patients. RESULTS: The median patient age was 61 years and median serum prostate-specific antigen (PSA) was 8.79 ng/mL. The mean period between transplantation and diagnosis of prostate cancer was 136 months. The sources for the kidney transplants included 10 living and 3 deceased donors. Biopsies indicated that the Gleason scores were 7 in 10 patients and 8 to 10 in 3 patients. Meanwhile, the D'Amico risk classification indicated an intermediate risk in 9 patients and a high risk in 4 patients. Eight patients were at stage cT1 and 5 were at stage cT2. The surgical procedure was retropubic radical prostatectomy in one recipient, laparoscopic radical prostatectomy in 3 recipients, and robot-assisted radical prostatectomy in 9 RTRs. Intraoperative complications were not noted in any patient, although one patient demonstrated postoperative complications (Clavien grade ≥ 3). An indwelling urinary catheter was required in 3 patients for over 3 weeks due to delayed wound healing. Biochemical recurrence evaluated by PSA monitoring occurred in four patients. Postoperative graft function was stable in all but one patient who required resumption of dialysis before prostatectomy; however, all patients are alive at the time of publication with 12 patients showing well-functioning renal allografts. CONCLUSION: Prostatectomy may be a feasible and effective technique as an initial treatment for RTRs with localized prostate cancer.

Excessive Oxidative Stress in the Synergistic Effects of Shikonin on the Hyperthermia-Induced Apoptosis.

BACKGROUND: Hyperthermia (HT) has been used widely for cancer therapy, and the development of modern devices has made it more efficient. Shikonin (SHK) is a natural naphthoquinone derivative from a Chinese herb. Although the anticancer properties of SHK are evident, the underlying molecular mechanisms are not fully understood. OBJECTIVE: In this study, the effects of combining low doses of SHK with mild HT were investigated in the U937 cell line. METHODS: The cells were subjected to HT at 44°C for 10 min with or without SHK pretreatment, and parameters reflecting apoptosis, ROS generation and intracellular calcium elevation were evaluated by using DNA fragmentation, flow cytometry, and western blot analyses. RESULTS: SHK 0.5 µM significantly enhanced HT-induced apoptosis as indicated by DNA fragmentation and caspase-3 activation with increased generation of ROS and elevation of intracellular calcium. The combined treatment also synergistically activated proapoptotic proteins and inactivated anti-apoptotic proteins. Furthermore, the phosphorylation of JNK and PKC- δ and the dephosphorylation of ERK and AKT were the upstream effects that may have compounded the induction of apoptosis. The modulatory effects of HT and SHK were abrogated with the employment of NAC and JNK-IN-8 by inactivating the MAPK pathway and cleavage of caspase-3. Intracellular calcium was also elevated and was found to be responsible for the induction of cell death evident by the DNA fragmentation with or without the employment of BAPTA-AM. CONCLUSION: Conclusively, this study provides persuasive evidence that SHK in combination with HT is a propitious therapeutic way for augmentation of apoptosis and hence suggest a novel strategy for treating cancers.

A rare case of fetal extensive intracranial hemorrhage and whole-cerebral hypoplasia due to latent maternal vitamin K deficiency.

We present here a late preterm infant with extensive brain lesions resulting from vitamin K deficiency. A female infant was born after 35 weeks of gestation by emergent cesarean section because of non-reassuring fetal status. Her mother had severe eating disorder and recurrent vomiting since early pregnancy. She was immediately intubated and ventilated because she was extremely pale, hypotonic, and non-reactive. Cerebral magnetic resonance imaging immediately after birth showed intraparenchymal hemorrhage in the left frontal lobe and cerebellum, marked cerebral edema, and cerebellar hypoplasia. Coagulation studies of the infant showed hepaplastin test <5%, prolonged PT and APTT, and a marked elevation of protein induced by vitamin K absence or antagonist-II. This case highlighted a potential risk of intracranial bleeding due to maternal vitamin K deficiency and difficulty in its prediction before delivery. Vitamin K supplementation to high risk mothers might be indispensable for preventing severe fetal vitamin K deficiency. Even when coagulation studies in mothers is normal, it is imperative to provide vitamin K supplementation for total protection.