Updated evidence of the effectiveness and safety of transanal drainage tube for the prevention of anastomotic leakage after rectal low anterior resection: a systematic review and meta-analysis.

BACKGROUNDS: Anastomotic leakage (AL) represents a major complication after rectal low anterior resection (LAR). Transanal drainage tube (TDT) placement offers a potential strategy for AL prevention; however, its efficacy and safety remain contentious. METHODS: A systematic review and meta-analysis were used to evaluate the influence of TDT subsequent to LAR as part of the revision of the surgical site infection prevention guidelines of the Japanese Society of Surgical Infectious Diseases (PROSPERO registration; CRD42023476655). We searched each database, and included randomized controlled trials (RCTs) and observational studies (OBSs) comparing TDT and non-TDT outcomes. The main outcome was AL. Data were independently extracted by three authors and random-effects models were implemented. RESULTS: A total of three RCTs and 18 OBSs were included. RCTs reported no significant difference in AL rate between the TDT and non-TDT groups [relative risk (RR): 0.69, 95% confidence interval (CI) 0.42-1.15]. OBSs reported that TDT reduced AL risk [odds ratio (OR): 0.45, 95% CI 0.31-0.64]. In the subgroup excluding diverting stoma (DS), TDT significantly lowered the AL rate in RCTs (RR: 0.57, 95% CI 0.33-0.99) and OBSs (OR: 0.41, 95% CI 0.27-0.62). Reoperation rates were significantly lower in the TDT without DS groups in both RCTs (RR: 0.26, 95% CI 0.07-0.94) and OBSs (OR: 0.40, 95% CI 0.24-0.66). TDT groups exhibited a higher anastomotic bleeding rate only in RCTs (RR: 4.28, 95% CI 2.14-8.54), while shorter hospital stays were observed in RCTs [standard mean difference (SMD): -0.44, 95% CI -0.65 to -0.23] and OBSs (SMD: -0.54, 95% CI -0.97 to -0.11) compared with the non-TDT group. CONCLUSIONS: A universal TDT placement cannot be recommended for all rectal LAR patients. Some patients may benefit from TDT, such as patients without DS creation. Further investigation is necessary to identify the specific beneficiaries.

A novel missense mutation affecting the same amino acid as the recurrent PACS1 mutation in Schuurs-Hoeijmakers syndrome.

A novel causative variant (c.608G>A, p.Arg203Gln) in PACS1.

PRUNE1-related disorder: Expanding the clinical spectrum.

Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (NMIHBA) (OMIM #617481) is an autosomal recessive disease characterized by progressive microcephaly, plagiocephaly, hypotonia, spastic quadriparesis, global developmental delay, intellectual disability, optic features and abnormal brain magnetic resonance imaging (MRI). NMIHBA was recently reported to be caused by PRUNE1 mutations. Eight mutations have been reported in 13 unrelated families. Here, we report 3 PRUNE1 mutations in 1 Caucasian and 3 Japanese families. One recurrent missense mutation (p.Asp106Asn) was previously reported in Turkish and Italian families, while the other 2 mutations (p.Leu18Serfs*8 and p.Cys180*) are novel. We also show that mutant PRUNE1 mRNA can be subject to nonsense-mediated mRNA decay. The patients presented in this study showed atypical NMIHBA phenotypes with no progressive microcephaly. Furthermore, one Caucasian case had significant macrocephaly; therefore, patients with PRUNE1 mutations can exhibit a broad and heterogeneous spectrum of phenotypes.

Novel biallelic SZT2 mutations in 3 cases of early-onset epileptic encephalopathy.

The seizure threshold 2 (SZT2) gene encodes a large, highly conserved protein that is associated with epileptogenesis. In mice, Szt2 is abundantly expressed in the central nervous system. Recently, biallelic SZT2 mutations were found in 7 patients (from 5 families) presenting with epileptic encephalopathy with dysmorphic features and/or non-syndromic intellectual disabilities. In this study, we identified by whole-exome sequencing compound heterozygous SZT2 mutations in 3 patients with early-onset epileptic encephalopathies. Six novel SZT2 mutations were found, including 3 truncating, 1 splice site and 2 missense mutations. The splice-site mutation resulted in skipping of exon 20 and was associated with a premature stop codon. All individuals presented with seizures, severe developmental delay and intellectual disabilities with high variability. Brain MRIs revealed a characteristic thick and short corpus callosum or a persistent cavum septum pellucidum in each of the 2 cases. Interestingly, in the third case, born to consanguineous parents, had unexpected compound heterozygous missense mutations. She showed microcephaly despite the other case and previous ones presenting with macrocephaly, suggesting that SZT2 mutations might affect head size.

Detection of copy number variations in epilepsy using exome data.

Epilepsies are common neurological disorders and genetic factors contribute to their pathogenesis. Copy number variations (CNVs) are increasingly recognized as an important etiology of many human diseases including epilepsy. Whole-exome sequencing (WES) is becoming a standard tool for detecting pathogenic mutations and has recently been applied to detecting CNVs. Here, we analyzed 294 families with epilepsy using WES, and focused on 168 families with no causative single nucleotide variants in known epilepsy-associated genes to further validate CNVs using 2 different CNV detection tools using WES data. We confirmed 18 pathogenic CNVs, and 2 deletions and 2 duplications at chr15q11.2 of clinically unknown significance. Of note, we were able to identify small CNVs less than 10 kb in size, which might be difficult to detect by conventional microarray. We revealed 2 cases with pathogenic CNVs that one of the 2 CNV detection tools failed to find, suggesting that using different CNV tools is recommended to increase diagnostic yield. Considering a relatively high discovery rate of CNVs (18 out of 168 families, 10.7%) and successful detection of CNV with <10 kb in size, CNV detection by WES may be able to surrogate, or at least complement, conventional microarray analysis.

Crystallization tendencies of modelled Lennard-Jones liquids with different attractions.

Molecular dynamics simulations are performed on simple models composed of monoatomic Lennard-Jones atoms for which the repulsive interaction is the same but the attractive part is tuned. We investigate the precise role of the attractive part of the interaction potential on different structural, dynamical, and thermodynamical properties of these systems in the liquid and crystalline states. It includes crystallization trends for which the main physical ingredients involved have been computed: the diffusion coefficient, the Gibbs energy difference between the liquid and the crystalline state, and the crystal-liquid interfacial free energy. Results are compared with predictions from the classical nucleation theory including transient and steady-state regimes at moderate and deeper undercooling. The question of the energetic and entropic impact of the repulsive and attractive part of the interaction potential towards crystallization is also addressed.

A case of atypical Kabuki syndrome arising from a novel missense variant in HNRNPK.

A novel causative variant (c. 464T>C, p.Leu155Pro) in the heterogeneous nuclear ribonucleoprotein K (HNRNPK) gene.

Association of Finger Tapping Movements with Frailty Status in older Japanese Adults: A Cross-Sectional Study.

BACKGROUND: Finger tapping impairment and frailty share overlapping pathophysiology and symptoms in older adults, however, the relationship between each other has not been previously studied. OBJECTIVES: To investigate how finger tapping movements correlate with frail status in older Japanese adults. DESIGN, SETTING, AND PARTICIPANTS: Data were from a cross-sectional study called the Cognition and Activity in Rural Environment of Hokkaido Senior Survey 2018. A total of 244 community-dwelling older adults (mean age 75.3 years) were included. MEASUREMENTS: Participants underwent physical examinations, gait and finger tapping tests, and completed self-administered questionnaires. Frailty was assessed using Fried's frailty phenotype, and factor analysis was conducted to extract relevant finger tapping factors. Multinomial logistic regression was employed to analyze associations, generating adjusted odds ratios. RESULTS: Of the participants, 18 were frail, and 145 pre-frail. Analysis identified three distinct finger tapping patterns: "Range of Motion - Nondominant Hand," "Variability - Dominant Hand - Anti," and "Variability - Nondominant Hand - Anti." These patterns showed significant associations with aspects of Fried's frailty phenotype, particularly low physical activity (P = 0.002), weakness (P = 0.003), and slowness (P = 0.004). A larger range of motion in the nondominant hand correlated with a lower frailty risk (Odds Ratio: 0.09, 95% CI: 0.02-0.46), while higher variability in the same hand increased the risk of pre-frailty (Odds Ratio: 2.19, 95% CI: 1.09-4.39). CONCLUSION: Finger tapping movements are significantly associated with frailty status as determined by Fried's phenotype. The findings underscore the importance of further longitudinal studies to understand the relationship between motor function and frailty.

The effectiveness of fascial closure with antimicrobial-coated sutures in preventing incisional surgical site infections in gastrointestinal surgery: a systematic review and meta-analysis.

The aim of this study was to conduct a systematic review and meta-analysis of the efficacy of fascial closure using antimicrobial-sutures specifically for the prevention of surgical site infections (SSIs) in gastrointestinal surgery, as part of the revision of the SSI prevention guidelines of the Japanese Society of Surgical Infectious Diseases (JSSI). We searched CENTRAL, PubMed and ICHUSHI-Web in May 2023, and included randomized controlled trials (RCTs) comparing antimicrobial-coated and non-coated sutures for fascial closure in gastrointestinal surgery (PROSPERO No. CRD42023430377). Three authors independently screened the RCTs. We assessed the risk of bias and the GRADE criteria for the extracted data. The primary outcome was incisional SSI and the secondary outcomes were abdominal wall dehiscence and the length of postoperative hospital stay. This study was supported partially by the JSSI. A total of 10 RCTs and 5396 patients were included. The use of antimicrobial-coated sutures significantly lowered the risk of incisional SSIs compared with non-coated suture (risk ratio: 0.79, 95% confidence intervals: 0.64-0.98). In subgroup analyses, antimicrobial-coated sutures reduced the risk of SSIs for open surgeries, and when monofilament sutures were used. Antimicrobial-coated sutures did not reduce the incidence of abdominal wall dehiscence and the length of hospital stay compared with non-coated sutures. The certainty of the evidence was rated as moderate according to the GRADE criteria, because of risk of bias. In conclusion, the use of antimicrobial-coated sutures for fascial closure in gastrointestinal surgery is associated with a significantly lower risk of SSI than non-coated sutures.

Association between skin suture devices and incidence of incisional surgical site infection after gastrointestinal surgery: systematic review and network meta-analysis.

BACKGROUND: Surgical site infections (SSIs) are common complications after abdominal surgery. AIM: To compare which suture devices could reduce the incidence of incisional surgical site infections (SSIs) after gastrointestinal surgery using a systematic review and network meta-analysis. METHODS: The CENTRAL, PubMed, and ICHUSHI-Web databases were searched from January 1st, 2000, to December 31st, 2022, for randomized clinical trials (RCTs) comparing the incidence of incisional SSI after gastrointestinal surgery among patients treated with different surgical suture devices, including non-absorbable sutures, absorbable sutures, skin staplers, and tissue adhesives (last searched in August 23th, 2023). The risk of bias was assessed using the criteria of the Cochrane Handbook for Systematic Reviews of Interventions. To estimate the pooled odds ratios (ORs) for each comparison, a fixed-effect inverse-variance model based on the Mantel-Haenszel approach was employed. FINDINGS: A total of 18 RCTs with 5496 patients were included in this study. The overall SSIs in absorbable sutures were significantly lower than those in skin staplers (OR: 0.77; 95% confidence intervals (CI): 0.63-0.95) and non-absorbable sutures (OR: 0.62; 95% CI: 0.39-0.99), whereas SSIs in absorbable sutures were not significantly different from the SSIs in tissue adhesive. The highest P-score was 0.91 for absorbable sutures. A funnel plot for estimating the heterogeneity of the studies revealed that a publication bias would be minimal (Egger test, P = 0.271). CONCLUSION: This study showed that absorbable sutures reduced incisional SSIs in gastrointestinal surgical operations compared to any other suture devices.

Determination of cooperatively rearranging regions in a binary glass former.

Cooperative motions are important for understanding the divergence of viscosity of glassy materials at a finite temperature, since the elementary process of the structural relaxation occurs within the smallest cooperative region as suggested by Adam and Gibbs. On the basis of the definition of a cooperatively rearranging region (CRR) by Adam and Gibbs and by Odagaki, we determine the size of CRR for the Kob-Andersen model as a function of temperature using molecular dynamics simulations. We first confine particles in a spherical region and, varying the radius of that region, we determine the CRR size as the smallest radius of the region in which particles can change their relative positions. The size of the CRR increases as the temperature is reduced and seems to diverge below the glass transition temperature. The temperature dependence of the number of particles in the CRR obeys the equation derived from the Adam-Gibbs relation and the Vogel-Fulcher-Tammann equation.

Identification of independent APP locus duplication in Japanese patients with early-onset Alzheimer disease.

BACKGROUND: The occurrence of duplications of the amyloid precursor protein gene (APP) has been described in European families with early-onset familial Alzheimer disease (EO-FAD) and cerebral amyloid angiopathy. However, the contribution of APP duplication to the development of AD in other ethnic populations remains undetermined. METHODS: The occurrence of APP duplication in probands from 25 families with FAD and 11 sporadic EO-AD cases in the Japanese population was examined by quantitative PCR and microarray-based comparative genomic hybridisation analyses. APP expression level was determined by real-time quantitative reverse-transcription (RT) PCR analysis using mRNA extracted from the peripheral blood of the patients. RESULTS: We identified APP locus duplications in two unrelated EO-FAD families. The duplicated genomic regions in two patients of these families differed from each other. No APP duplication was found in the late-onset FAD families or sporadic EO-AD patients. The patients with APP duplication developed insidious memory disturbance in their fifties without intracerebral haemorrhage and epilepsy. Quantitative RT-PCR analysis showed the increased APP mRNA expression levels in these patients compared with those in age- and sex-matched controls. CONCLUSIONS: Our results suggest that APP duplication should be considered in patients with EO-FAD in various ethnic groups, and that increased APP mRNA expression level owing to APP duplication contributes to AD development.

Alu-related 5q35 microdeletions in Sotos syndrome.

Haploinsufficiency of the NSD1 gene due to 5q35 microdeletions or intragenic mutations causes Sotos syndrome (SoS). In 46 of the 49 Japanese deletion cases, common deletion breakpoints were located at two flanking low copy repeats (LCRs), implying that non-allelic homologous recombination (NAHR) between LCRs is the major mechanism for the common deletion. In the other three cases of atypical deletions, the mechanism(s) of deletions remains unanswered. We characterized the atypical microdeletions using fluorescence in situ hybridization (FISH), quantitative real-time polymerase chain reaction (qPCR), and Southern blot hybridization. All the deletion breakpoints in the three cases were successfully determined at the nucleotide level. Two deletions are 1.07 Mb (SoS19) and 1.23 Mb (SoS109) in size, and another consisted of two deletions with sizes of 28 kb and 0.72 Mb, intervened by an intact 29-kb segment (SoS44). All deletions were smaller than a typical 1.9-Mb common deletion. Alu elements were identified in both deletion breakpoints in SoS19, one of deletion breakpoints in SoS109, and both deletion breakpoints of the proximal 28-kb deletion in SoS44. Alu-mediated NAHR is strongly suggested at least in two of atypical deletions. Finally, qPCR is a very useful method to determine deletion breakpoints even in repeat-related regions.

Quantitative analysis of the effect of colony-stimulating factors on human marrow progenitor growth in liquid-suspension cultures: application of limiting dilution assay.

Proliferation of human marrow progenitors in liquid cultures can be quantitated by limiting dilution clonal analysis (LDA) of progenitors in microwells. In this study, we have used LDA to study the effect of purified native or recombinant granulocyte colony-stimulating factors (G-CSFs) and recombinant granulocyte-macrophage CSF (GM-CSF) on progenitor growth. These results were compared to those of simultaneous cultures in methylcellulose. In LDA, single-hit kinetics were obtained with up to 500 U/ml of the recombinant preparation. In LDA with recombinant GM-CSF, progenitor growth conformed to single-hit kinetics from 100 to 2000 U/ml with maximum progenitor frequency at 500 U/ml. In simultaneous methylcellulose cultures with recombinant GM-CSF, colony formation reached a plateau at 100 U/ml. In LDA, purified native G-CSF was shown to support progenitor growth with single-hit kinetics at 100 U/ml, but at greater concentrations (greater than 150 U/ml), it suppressed progenitor growth with almost complete inhibition at a concentration of 200 U/ml. However, this dose-response effect was not observed in either simultaneous methylcellulose culture with G-CSF or in LDA with a purified recombinant preparation of the corresponding G-CSF. In methylcellulose cultures, colony formation reached a maximum at 100 U/ml and maintained a plateau up to 1000 U/ml. Hence, liquid culture allowed detection of contaminating suppressive activity in the G-CSF preparation that was not detected by methylcellulose assay. LDA may be more sensitive than methylcellulose culture for screening factors regulating human hematopoietic cell growth.

Analysis of two pharmacologically predicted endothelin B receptor subtypes by using the endothelin B receptor gene knockout mouse.

1. This study was performed to clarify whether the endothelin (ET) receptor subtypes mediating two pharmacologically heterogeneous response to ETH receptor agonists in normal mice are the product(s) of a single ETB receptor gene. 2. Vasodilator responses to sarafotoxin S6c (S6c) in the thoracic aorta and contractile responses to ET-1 and IRL1620 in the stomach were examined in tissues from normal and ETB receptor gene knockout mice, in the absence and presence of an ETA receptor antagonist, BQ-123, or an ETA/ETB receptor antagonist, PD142893. 3. In the normal mouse aorta precontracted with phenylephrine, S6c (0.1-100 nM) caused concentration-dependent relaxations (pD2 = 8.4). BQ-123 had no effect on these responses. However, PD142893 almost abolished the relaxations induced by 0.1-300 nM S6c. 4. In aortae taken from ETB receptor gene knockout mice, S6c up to 1 microM failed to cause relaxations, confirming that ETB receptors are involved in mediating this response. 5. In normal mouse gastric fundus, 0.1 nM-1 microM ET-1, S6c or IRL1620 caused dose-dependent, BQ-123-insensitive contractions, which were much more resistant to PD142893 than S6c-induced relaxations of the aorta. The pD2 values for S6c in the absence and presence of PD142893 (10 microM) were 8.12 +/- 0.11 and 7.70 +/- 0.11, respectively. 6. In the gastric fundus of the ETB receptor gene knockout mouse, S6c and IRL1620 caused no contractions. ET-1 (0.1 nM-1 microM) caused contractions sensitive to both BQ-123 and PD142893, indicating that only ETA receptors mediate ET-1-induced contractions of the knockout mouse gastric fundus. 7. Since both the PD142893-sensitive vasodilator response of the aorta and the PD142893-resistant contractile response of the gastric fundus to S6c were completely absent in the ETB receptor gene knockout mouse, we conclude that the two pharmacologically heterogeneous responses to S6c are mediated by receptors derived from the same ETB receptor gene.

The 5'-flanking region of the human dopamine beta-hydroxylase gene promotes neuron subtype-specific gene expression in the central nervous system of transgenic mice.

Dopamine beta-hydroxylase (DBH, EC 1.14.17.1) catalyzes the conversion of dopamine to norepinephrine, the third step of catecholamine biosynthesis. We have previously created transgenic mice harboring a chimeric gene consisting of the 4-kb DNA fragment of the human DBH gene promoter and the human phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) cDNA, to express PNMT in norepinephrine- and epinephrine-producing cells in the brain, sympathetic ganglia, and adrenal medullary chromaffin cells (Kobayashi et al., Proc. Natl. Acad. Sci. U.S.A., 89 (1992) 1631-1635). In this paper, we produced for the first time the antibody that specifically detects human PNMT, but not mouse PNMT, with the synthetic oligopeptide characteristic of the human PNMT sequence, and used this antibody to investigate the cells expressing human PNMT in transgenic mice. Immunohistochemical analysis of transgenic mice showed typical expression of human PNMT immunoreactivity in norepinephrinergic and epinephrinergic neurons in brain, as well as norepinephrine- and epinephrine-producing cells in the adrenal gland, indicating that the 4-kb 5'-flanking region is essential for the tissue-specific expression of the DBH gene. We also detected the ectopic expression in some DBH-immunonegative cells in the olfactory bulb of transgenic mice.

Recovery of mRNA expression of tryptophan 2,3-dioxygenase and serine dehydratase in long-term cultures of primary rat hepatocytes.

Expression of tryptophan 2,3-dioxygenase (TO) and serine dehydratase (SDH) has not previously been maintained or re-induced in long-term cultured hepatocytes. In the present study, we succeeded in inducing expression of TO and SDH mRNAs in adult rat hepatocytes cultured in serum-free L-15 medium supplemented with epidermal growth factor and 2% dimethyl sulfoxide (DMSO). After the start of culture, the expression of TO mRNA rapidly disappeared and at 96 h it was less than 10% of that at isolation. However, after the addition of 2% DMSO from 96 h, the transcript level gradually increased and reached about 40% of that of the isolated cells at day 14. In addition, the expression of TO mRNA was enhanced in cells treated with both 10(-5) M dexamethasone and 10(-7) M glucagon. In contrast, the expression of SDH mRNA decreased very rapidly and we could not detect it after 24 h of culture. Furthermore, 2% DMSO failed to induce it. However, when both 10(-5) M dexamethasone and 10(-7) M glucagon were added to the culture medium at day 9, we observed dramatic induction of SDH mRNA 24 h later. Primary hepatocytes cultured by this method could express and maintain highly differentiated hepatic functions for a long time. Thus, this in vitro system is suitable for the investigation of hepatic functions.

Respiratory reflex responses to stimulation of tracheal mucosa in enflurane-anesthetized humans.

We investigated respiratory reflex responses to tracheal mucosa stimulation induced by injection of distilled water in 13 female patients under three different depths of enflurane anesthesia (0.7, 1.0, and 1.3 minimum alveolar concentration). Detailed analysis of the types of reflex responses revealed that there are at least six different responses: 1) the apneic reflex, 2) the expiration reflex, 3) spasmodic, panting breathing, 4) the cough reflex, 5) slowing of breathing, and 6) rapid, shallow breathing. Among these reflex responses, the cough reflex was the most sensitive and the apneic reflex followed by slowing of breathing was the most resistant to deepening anesthesia, whereas the sensitivity of other types of reflex responses was in between. Our results indicate that the types of respiratory reflex responses to tracheal mucosa stimulation are associated with depths of anesthesia and that the differences in sensitivity to anesthesia may be a valuable sign in clinical assessment of depth of anesthesia.