Presoaking Grafts in Vancomycin Does Not Impair Graft-Bone Healing in a Rat Anterior Cruciate Ligament Reconstruction Model.

BACKGROUND: The vancomycin presoaking technique (wherein grafts are treated with a vancomycin solution [VS] for anterior cruciate ligament reconstruction [ACLR]) reduces the infection rate after ACLR. However, the effects of this technique on graft-bone healing have not been fully elucidated. PURPOSE: To investigate the effects of vancomycin presoaking on graft-bone healing in a rat ACLR model. STUDY DESIGN: Controlled laboratory study. METHODS: Long flexor digitorum longus tendons were obtained from 9 Wistar rats, and each was randomly allocated to the normal saline (NS) or VS groups. The grafts were immersed in sterile saline for 30 minutes in the NS group and in a 5-mg/mL VS in the VS group. The presence of time-zero graft bacterial contamination was confirmed, and the grafts were incubated in Fluidised Thioglycollate Broth for 2 weeks. ACLR was performed on the right knees of 65 male Wistar rats using the flexor digitorum longus tendons. Each graft was similarly treated. Biomechanical testing, micro-computed tomography, and histological evaluations were performed 4 and 12 weeks postoperatively. RESULTS: The VS group showed significantly reduced graft contamination at time zero (P = .02). The mean maximum loads to failure were 13.7 ± 8.2 N and 11.6 ± 4.8 N in the NS and VS groups, respectively, at 4 weeks (P = .95); and 23.2 ± 13.2 N and 30.4 ± 18.0 N in the NS and VS groups, respectively, at 12 weeks (P = .35). Regarding micro-computed tomography, the mean bone tunnel volumes were 3.76 ± 0.48 mm3 and 4.40 ± 0.58 mm3 in the NS and VS groups, respectively, at 4 weeks (P = .41); and 3.51 ± 0.38 mm3 and 3.67 ± 0.35 mm3 in the NS and VS groups, respectively, at 12 weeks (P = .54). Histological semiquantitative examination revealed no clear between-group differences at any time point. CONCLUSION: Presoaking grafts in vancomycin in a rat ACLR model demonstrated no discernible adverse effects on short- and midterm biomechanical, radiological, and histological investigations. CLINICAL RELEVANCE: The findings provide guidance for surgeons when considering this technique.

Association between precautionary behaviors against coronavirus disease and psychosocial factors in outpatients with a pre-existing disease and their attendants.

Aim: The spread of the novel coronavirus infection (coronavirus disease 2019 [COVID-19]) has caused behavioral changes and mental illness in patients and their attendants during its early phase. The present study aimed to examine the association between precautionary behaviors against COVID-19 and psychosocial factors in outpatients with pre-existing disease and their attendants. Methods: We conducted a cross-sectional paper-based questionnaire survey in Chiba University Hospital on 1019 patients and 513 attendants, and a web-based questionnaire survey in Japan on 3981 individuals from the general population. We evaluated the participants' anxiety about COVID-19, depression, health anxiety, and precautionary behaviors. Results: Regarding knowledge and anxiety about COVID-19, the protective factors for the high precautionary behaviors group were knowledge of COVID-19 (odds ratio [OR] = 1.178, 95% confidence interval [CI]: 1.099-1.263), anxiety about the spread of COVID-19 (OR = 1.348, 95% CI: 1.243-1.461), and anxiety about infecting someone with COVID-19 (OR = 1.135, 95% CI: 1.039-0.239). Regarding psychosocial factors, the protective factors for the high precautionary behaviors group were patients (OR = 1.759, 95% CI: 1.056-2.929), their attendants (OR = 3.892, 95% CI: 1.416-10.700), health anxiety (OR = 2.005, 95% CI: 1.451-2.772), and nondepression states (OR = 1.368, 95% CI: 1.004-1.864). Conclusion: Our findings suggest that patients and their attendants may perform high precautionary behaviors. Health anxiety and nondepression states may be associated with high precautionary behaviors.

Risk factors for early-phase clozapine discontinuation: A nested case-control study.

OBJECTIVES: Safe and efficient methods for introducing clozapine to patients with treatment-resistant schizophrenia (TRS) are needed. We investigated risk factors for clozapine discontinuation in the early phase of its introduction. METHODS: We conducted a nested case-control study at 14 psychiatric hospitals in Chiba, Japan. Data from pre-registered TRS patients were collected at 7 time points within 12 weeks before and after the start of clozapine introduction. We examined the demographic data, prior and concomitant psychotropic drugs, strategies for switching from prior antipsychotics, and blood test and Global Assessment of Function results. The Clinical Global Impression-Severity Scale was retrospectively scored at 12 weeks before and after clozapine introduction. RESULTS: Of 228 patients, clozapine treatment was continued in 213 (93.4 %) and discontinued in 15 (6.6 %) patients within 12 weeks. Clinical symptoms were improved to mild symptoms with a response rate of 14.9 %. Prior antipsychotics and concomitant psychotropic drugs except for mood stabilizers were significantly decreased. Histories of smoking (OR = 3.32, 95 %CI: 1.11-9.93) and antipsychotic treatment at chlorpromazine-equivalent doses <1200 mg within the past 5 years (OR = 3.93, 95 %CI: 1.24-12.50), but not antipsychotic switching strategy, were associated with clozapine discontinuation. Eosinophilia was the most frequent reason for discontinuation (n = 3, 20 %) and was associated with concomitant valproate at 4 weeks after the introduction. CONCLUSION: Clozapine is an effective option for TRS patients (especially those treated with higher doses of prior antipsychotics) in Japan. Clinicians should be cautious about concomitant valproate in the early phase of clozapine introduction due to a high risk of eosinophilia.

Identification of psychological features and development of an assessment tool for event-related psychological distress after experiencing non-traumatic stressful events.

Stressful events in daily life that are non-traumatic (e.g., family-, school-, work-, interpersonal-, and health-related problems) frequently cause various mood disturbances. For some people, being exposed to non-traumatic but stressful events could trigger the onset and relapse of mood disorders. Furthermore, non-traumatic stressful events also cause event-related psychological distress (ERPD), similar to that of post-traumatic stress disorder (PTSD; i.e., intense intrusive imagery or memory recall, avoidance, and hyperarousal) in the general population and individuals with mood disorders. However, previous ERPD studies only showed that people with ERPD display PTSD-like symptoms after non-traumatic experiences; they failed to get to the crux of the matter by only utilizing trauma- or PTSD-related assessment tools. We thus aimed to identify the psychological phenomena and features of ERPD after individuals experienced non-traumatic stressful events, and to develop and validate an appropriate ERPD assessment tool. First, we conducted a qualitative study to obtain the psychological features through interviews with 22 individuals (mean age = 41.50 years old, SD = 12.24) with major depressive disorder or bipolar disorder. Second, in the quantitative component, we implemented a web-based survey with 747 participants of the general population (mean age = 41.96 years old, SD = 12.64) by using ERPD-related questionnaires created based on the qualitative study; then, we examined the reliability and validity of the ERPD assessment tool. Results yielded that the psychological features of ERPD comprised four factors: feelings of revenge, rumination, self-denial, and mental paralysis. These were utilized in the developed 24-item measure of ERPD-a novel self-report assessment tool. For various professionals involved in mental healthcare, this tool can be used to clarify and assess psychological phenomena in people with ERPD.

A randomized-controlled trial of blonanserin and olanzapine as adjunct to antipsychotics in the treatment of patients with schizophrenia and dopamine supersensitivity psychosis: The ROADS study.

Dopamine supersensitivity psychosis (DSP) is a key factor contributing to the development of antipsychotic treatment-resistant schizophrenia. We examined the efficacy and safety of blonanserin (BNS) and olanzapine (OLZ) as adjuncts to prior antipsychotic treatment in patients with schizophrenia and DSP in a 24-week, multicenter (17 sites), randomized, rater-blinded study with two parallel groups (BNS and OLZ add-on treatments) in patients with schizophrenia and DSP: the ROADS Study. The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 24. Secondary outcomes were changes in the PANSS subscale scores, Clinical Global Impressions, and Extrapyramidal Symptom Rating Scale (ESRS), and changes in antipsychotic doses. The 61 assessed patients were allocated into a BNS group (n = 26) and an OLZ group (n = 29). The PANSS total scores were reduced in both groups (mean ± SD: -14.8 ± 24.0, p = 0.0042; -10.5 ± 12.9, p = 0.0003; respectively) with no significant between-group difference (mean, -4.3, 95 %CI 15.1-6.4, p = 0.42). The BNS group showed significant reductions from week 4; the OLZ group showed significant reductions from week 8. The ESRS scores were reduced in the BNS group and the others were reduced in both groups. The antipsychotic monotherapy rates at the endpoint were 26.3 % (n = 6) for BNS and 23.8 % (n = 5) for OLZ. The concomitant antipsychotic doses were reduced in both groups with good tolerability. Our results suggest that augmentations with BNS and OLZ are antipsychotic treatment options for DSP patients, and BNS may be favorable for DSP based on the relatively quick responses to BNS observed herein.

The Effect of Grandmothers' Presence on the Provision of Multidisciplinary Perinatal Support for Pregnant and Postpartum Women with Psychosocial Problems.

BACKGROUND: Pregnant and postpartum women with psychosocial problems are prone to face limited or absent perinatal functional support from biological grandmothers due to familial dysfunction. The study aimed to investigate whether the involvement and presence of biological maternal grandmothers providing practical support for their pre/postnatal daughters (ie, pregnant women) during the perinatal period may influence the number of support services provided by multidisciplinary agencies, including child consultation centers and municipal offices. PARTICIPANTS AND METHODS: This is a retrospective cohort study based on the medical records of all pregnant women with psychosocial problems that visited, gave birth, and received intervention from the hospital-based child protection unit at the Chiba University Hospital between February 2018 to March 2019. The primary outcome was to identify whether there was a difference in the number of multidisciplinary agencies providing perinatal support between pregnant women with and without the presence of functional support from biological maternal grandmothers during the perinatal period. RESULTS: We identified 114 pregnant and postpartum women with psychosocial problems. Seventy-six of these participants (66.7%) had functional support from their biological maternal grandmothers during the perinatal period, and 38 participants (33.3%) did not. The number of agencies involved with participants who lacked functional support was significantly higher than participants with functional support (t(55.14) = 2.98, p < 0.01). This finding was consistent among pregnant and postpartum primipara participants (n = 70) (t(68) = 3.87, p < 0.001), but not multipara (n = 44). CONCLUSION: The findings indicate that the presence and functional support of biological maternal grandmothers influence the support that is needed from multidisciplinary perinatal support systems by pregnant and postpartum women with psychosocial problems. Primipara mothers without support from their own mothers may need greater multidisciplinary support.

Adrenal Rest Tumor of the Liver Preoperatively Diagnosed as Hepatocellular Carcinoma.

BACKGROUND: Hepatic adrenal rest tumors are rare and show similar findings to hepatocellular carcinoma (HCC). It is difficult to distinguish an adrenal rest tumor from HCC due to radiological similarity. We report a case of an adrenal rest tumor in the liver that mimicked HCC radiologically. CASE PRESENTATION: A 67-year-old female was referred to our hospital due to the finding of a hepatic mass. Enhanced computed tomography revealed a 17 mm well-defined tumor that was enhanced in the arterial phase and washed out in the portal and delayed phase in the posterosuperior subsegment of the right hepatic lobe, and HCC was suspected. We performed a subsegmental resection of the liver. Microscopic findings showed that the tumor was composed of pale cells, and tumor cells were aligned in alveolar or fascicular arrangements in a similar manner to features of adrenocortical tissue. Immunohistochemically, the tumor expressed synaptophysin and CD56. The final histopathologic diagnosis in this case was an adrenal rest tumor of the liver. CONCLUSIONS: An adrenal rest tumor is similar to HCC in radiological findings. This hepatic tumor should be added to the list of radiological differential diagnoses of hypervascular hepatic tumors.

Experimental investigation of chirp properties induced by signal amplification in quantum-dot semiconductor optical amplifiers.

We experimentally show the dynamic frequency chirp properties induced by signal amplification in a quantum-dot semiconductor optical amplifier (QD-SOA) for the first time. We also compare the red and blue chirp peak values and temporal chirp changes while changing the gain and injected signal powers of the QD-SOA with those of a common SOA.

Mutations in the FHA-domain of ectopically expressed NBS1 lead to radiosensitization and to no increase in somatic mutation rates via a partial suppression of homologous recombination.

Ionizing radiation induces DNA double-strand breaks (DSBs). Mammalian cells repair DSBs through multiple pathways, and the repair pathway that is utilized may affect cellular radiation sensitivity. In this study, we examined effects on cellular radiosensitivity resulting from functional alterations in homologous recombination (HR). HR was inhibited by overexpression of the forkhead-associated (FHA) domain-mutated NBS1 (G27D/R28D: FHA-2D) protein in HeLa cells or in hamster cells carrying a human X-chromosome. Cells expressing FHA-2D presented partially (but significantly) HR-deficient phenotypes, which were assayed by the reduction of gene conversion frequencies measured with a reporter assay, a decrease in radiation-induced Mre11 foci formation, and hypersensitivity to camptothecin treatments. Interestingly, ectopic expression of FHA-2D did not increase the frequency of radiation-induced somatic mutations at the HPRT locus, suggesting that a partial reduction of HR efficiency has only a slight effect on genomic stability. The expression of FHA-2D rendered the exponentially growing cell population slightly (but significantly) more sensitive to ionizing radiation. This radiosensitization effect due to the expression of FHA-2D was enhanced when the cells were irradiated with split doses delivered at 24-h intervals. Furthermore, enhancement of radiation sensitivity by split dose irradiation was not seen in contact-inhibited G0/G1 populations, even though the cells expressed FHA-2D. These results suggest that the FHA domain of NBS1 might be an effective molecular target that can be used to induce radiosensitization using low molecular weight chemicals, and that partial inhibition of HR might improve the effectiveness of cancer radiotherapy.

[Insertion of percutaneous transhepatic biliary endoprosthesis for unresectable lower cholangiocellular carcinoma following cholangitis due to endoscopic biliary plastic stent obstruction].

The patient was an 87-year-old woman who was diagnosed with atrial fibrillation, which was treated with an anticoagulant, and with chronic kidney disease. The patient was diagnosed as having liver dysfunction and lower cholangiocellular carcinoma (cStage I) on ultrasonography and magnetic resonance cholangiopancreatography. Since it was impossible to perform curative resection owing to the patient's decreased cardiac and renal function, we performed palliative endoscopic retrograde biliary drainage (ERBD) with a plastic stent (PS), and the patient was discharged 11 days later. However, the patient was readmitted because of fever (>38.0°C) and vomiting 124 days after ERBD. We assumed that the patient had developed cholangitis due to PS obstruction. Moreover, her blood culture was positive for Klebsiella pneumoniae. We were unable to replace the PS as the tumor had increased in size and hemorrhage from the papilla of Vater continued after the stent had been removed. The signs of inflammation improved after treatment of sepsis with antibiotics and immunoglobulins, and we performed percutaneous transhepatic cholangio drainage( PTCD) and eventually inserted a percutaneous transhepatic biliary endoprosthesis (PTBE) with an expandable metallic stent (EMS). The patient died 2 months later; no stent occlusion was observed. Our experience suggests that endoscopic biliary stents should be selected bearing in mind the patency of the stent and the prognosis.

[A case of successful radical resection of rectal cancer with neo-adjuvant chemoradiotherapy].

In cases of advanced rectal cancer, preoperative chemoradiotherapy( CRT) serves to improve the local control rate, survival rate, radical resection rate, and/or probability of sphincter muscle preservation. According to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer, preoperative CRT is the standard treatment for rectal cancer in Europe and the United States. However, there is insufficient evidence in support of its efficacy and safety in Japan, and therefore, CRT needs to be evaluated in properly designed clinical trials. Recently, several studies have reported on the efficacy of preoperative CRT in Japan. Herein, we report a case of rectal cancer in which radical resection was successfully performed with neo-adjuvant CRT.

[Preoperative chemotherapy for advanced gastric cancer].

In the present study, we evaluated the outcome of preoperative treatment with S-1 and CDDP for the treatment of advanced gastric cancer. Fifty-five cases of advanced gastric cancer received pre-operative treatment with S-1 and CDDP. The tumor control rate( PR and CR according to RECIST criteria) was 55%. The clinical response and histological response to the treatment and curative resection were closely related to favorable postoperative survival. We noted that patients who demonstrated CR or PR received S-1 as postoperative treatment, whereas those with SD or PD were more likely to receive paclitaxel as postoperative treatment. Preoperative treatment with S-1 and CDDP was not only an effective initial treatment, but also demonstrated favorable results in a S-1 in vivo sensitivity test.

[Hepatic arterial infusion with subsequent hepatectomy for a sigmoid colon cancer patient with hepatic metastases-a case report].

It is common to use systemic chemotherapy, instead of hepatic arterial infusion (HAI) of 5-fluorouracil (5-FU) or other cytotoxic agents, for unresectable hepatic metastases in colorectal cancer patients. Nevertheless, systemic administration of anticancer agents such as FOLFOX or FOLFIRI is sometimes difficult to continue for infirm patients. A 71-year-old female who had undergone sigmoidectomy for sigmoid colon cancer received HAI for 12 months because of big bilobar hepatic metastases and poor performance status. Thereafter, a two-stage hepatectomy(first, left lobe: second, S7+8 and S5) was performed successfully. She has been alive for 2.5 years after the first operation but with two small lung metastases in the left lobe. Because of bad performance status and her weak social and familial conditions, treatment with standard systemic chemotherapy could not be continued. In such cases, HAI should be performed if the metastases are limited to the liver.

RR-QT interval trend covariability for sudden cardiac death risk stratification.

This paper examines the feasibility of the trend covariability between QT and RR Intervals (QTIs and RRIs) be a novel mean of the sudden cardiac death (SCD) risk stratification. Twenty four hour beat to beat QTIs and RRIs are measured from Holter ECG recordings of 25 normal control subjects (SCD-C), 14 low SCD risk patients (SCD-L) with high blood pressure or light cardiac arrhythmia and 11 SCD high risk patients (SCD-H) with heart attack history. The Kalman filtering technique has been applied to decompose 24 hour short term mean QTIs and RRIs sequences into trend components and additive random variations. The correlation coefficients (TC-QT/RR) and cross entropies (TE-QT/RR) between the QT and RR trend signals are estimated. Cross entropy TE-QT/RR achieved the best stratification of subject groups. TE-QT/RR distribution for SCD-C, -L -H subject groups were 1.697 ± 0.058, 1.160 ± 0.099, 0.920 ± 0.067. The differences in entropy values are statistically significant for all classes pairs (SCD-H and -C (p<0.00001); -L and -C (p<0.001); -H and -L (p<0.05) The result indicates that the TE-QT/RR could be a novel index for the SCD risk stratification.

A method for characterizing circadian changes in QT intervals of diabetic patients.

This paper proposes a method to characterize circadian changes in QT intervals for diabetic studies. Although properties of QT intervals for diabetic patients are extensively studied, their circadian changes are not fully understood. Recently, the traditional cosinor method has been utilized for a study examining the relationship between QT circadian changes and the insulin resistance of the diabetic patients. For better characterization of the circadian change in QT intervals of this kind, spline smoothing technique applied to a decimated data set of QT intervals is proposed. New indices named QT circadian transition time (QTCT) and QT circadian transition amplitude (QTCA) associated with the subjects' awakening process are defined to characterize diabetic patients' condition. The method is applied to ten normal and fifteen type 2 diabetic patients. The proposed indices showed significantly lower values for type 2 diabetic patients compared to the control subjects indicating their effectiveness for the characterization.

Dancing on damaged chromatin: functions of ATM and the RAD50/MRE11/NBS1 complex in cellular responses to DNA damage.

In order to preserve and protect genetic information, eukaryotic cells have developed a signaling or communications network to help the cell respond to DNA damage, and ATM and NBS1 are key players in this network. ATM is a protein kinase which is activated immediately after a DNA double strand break (DSB) is formed, and the resulting signal cascade generated in response to cellular DSBs is regulated by post-translational protein modifications such as phosphorylation and acetylation. In addition, to ensure the efficient functioning of DNA repair and cell cycle checkpoints, the highly ordered structure of eukaryotic chromatin must be appropriately altered to permit access of repair-related factors to DNA. These alterations are termed chromatin remodeling, and are executed by a specific remodeling complex in conjunction with histone modifications. Current advances in the molecular analysis of DNA damage responses have shown that the auto-phosphorylation of ATM and the interaction between ATM and NBS1 are key steps for ATM activation, and that the association of ATM and NBS1 is involved in chromatin remodeling. Identification of novel factors which function in ubiquitination (RNF8, Ubc13, Rap80, etc.) has also enabled us to understand more details of the early stages in DNA repair pathways which respond to DSBs. In this review, the focus is on the role of ATM and the RAD50/MRE11/NBS1 complex in DSB response pathways, and their role in DSB repair and in the regulation of chromatin remodeling.

Relationship between fetal weight, placental growth and litter size in mice from mid- to late-gestation.

In mammals, the placenta, which consists of maternal and fetal components, is important in fetal development because it supplies the fetus with the nourishment it needs. We investigated the effects of placental growth and litter size on mouse fetal weights from mid- to late-gestation. The mean weight of male fetuses at 13.5 days post coitum (dpc) was larger than that of females. Although there was a significant correlation between fetal and placental weights in both males and females during mid-gestation (P<0.05), there was no correlation during late-gestation. However, a significant correlation was observed between litter size and fetal weights in both males and females at 17.5 dpc (P<0.05). These findings suggest that fetal weight is regulated by placental growth during mid-gestation, while the effects of litter size are more prominent towards late-gestation.