Early predictive factors and risk assessment for anastomotic leakage in patients undergoing low anterior resection for rectal cancer.

OBJECTIVE: Anastomotic leakage is a complication that creates significant concern in terms of postoperative morbidity and mortality after colorectal surgery. This study aimed to identify variables for detecting anastomotic leakage in those who had open, laparoscopic, or robotic low anterior resection for cancer and to explore their relationships. PATIENTS AND METHODS: A total of 283 patients who were diagnosed with rectal cancer and underwent low anterior resection were divided into two groups: those with and without anastomotic leakage. Demographic and clinical data were analyzed. Anastomotic leakage was detected in 23 of 283 patients who underwent low anterior resection. RESULTS: The postoperative analysis of the biochemical data of the patients showed statistically significant differences between the two groups in terms of C-reactive protein (Crp), albumin, lymphocytes, leukocytes, neutrophils, and their ratio. The performance of these parameters in predicting anastomotic leakage was statistically analyzed in the patient group with anastomotic leakage, and nomogram results were acquired. Immune system components and biomarkers were statistically tested, and nomogram results were obtained in rectal cancer patients. CONCLUSIONS: These parameters can be used together as a potential marker in anastomotic leakage. Further development of these variables has the potential to facilitate the timely detection and treatment of anastomotic leakage.

Incorporating health equity in the neurology curriculum: Our experience.

BACKGROUND: Social determinants of health (SDoH) are responsible for 80-90% of modifiable contributors to health, yet this material may not be covered in preclinical medical school neuroscience courses. OBJECTIVE: To describe how topics related to SDoH and inclusion, diversity, equity, anti-racism, and social justice (IDEAS) were incorporated into a preclinical neuroscience course. METHODS: IDEAS concepts and guided discussions were added to our existing case-based curriculum, and guest speakers were invited to discuss how these concepts are relevant in the field of neurology. RESULTS: Most students felt that content and discussions were integrated thoughtfully. Students also found it helpful to learn and observe how faculty address these topics in real-world cases. CONCLUSION: The additional content related to SDoH and IDEAS is feasible. Faculty with or without expertise in IDEAS concepts were able to utilize these cases and generate discussion without detracting from the neuroscience course material.

Sexual problems in MS: Sex differences and their impact on quality of life.

BACKGROUND: Low sexual function and satisfaction are common problems among people with multiple sclerosis (PwMS), but the literature on which patient variables are associated with these issues is inconsistent. OBJECTIVE: To investigate the associations between sexual function and satisfaction in PwMS with clinical, demographic, and patient-reported quality of life (QOL) measures and determine if sex differences exist. METHODS: This analysis includes PwMS enrolled in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB), who completed patient-reported outcome measures: Multiple Sclerosis Quality of Life-54 (MSQOL-54), Modified Fatigue Impact Scale (MFIS), and Center for Epidemiologic Studies Depression Scale (CES-D). Regression models were used to analyze associations between patient variables and function and satisfaction. Results were stratified by sex. Cross-sectional and longitudinal data were used. RESULTS: 702 PwMS (526 females,176 males, mean age 42.2 +/-11.1, median EDSS 1.5) were included in the cross-sectional analysis. Data from 341 PwMS were used in the three-year longitudinal analysis. Increasing age, disease duration, and disability were associated with reduced sexual function and satisfaction to the same degree in males and females. However, sex differences existed in the strength of associations with QOL variables. There was no significant longitudinal change in females or males. CONCLUSIONS: Age and disease duration were associated with reduced sexual function and satisfaction in males and females. In females, function was significantly associated with disability and satisfaction with fatigue. Males had stronger associations with sexual function in domains related to emotional well-being, health perceptions, and overall QOL. Males had stronger associations with satisfaction in emotional and social functioning and physical health domains. These findings can help better understand the multidimensional problems of sexual function and satisfaction in PwMS and better guide patient care.

Effect of pregnancy loss on MS disease activity.

OBJECTIVE: To evaluate the effect of pregnancy loss (PL) on MS disease activity. METHODS: Eleven women with first-trimester PLs were identified through a reproductive questionnaire. MS activity (MRI lesions and/or clinical relapses) was compared for the 12 months before conception and after PL. RESULTS: There was MS activity in 7/11 participants after, compared with 3/11 before PL (McNemar's test, p = .29), including MRI activity in 7/11 after, compared with 2/11 before PL (McNemar's test, p = .13). CONCLUSION: Larger studies are needed to confirm this observed trend of increased MS activity following PL.

Infectious Complications of Novel Multiple Sclerosis Therapies.

PURPOSE OF REVIEW: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system most often characterized by clinical relapses and periods of remission. RECENT FINDINGS: The past decade has seen a dramatic increase in disease-modifying therapies for MS. Fourteen FDA-approved immunomodulatory drugs are currently available, and more medications are in development. A growing number of reported opportunistic infections, including progressive multifocal leukoencephalopathy (PML), highlight the serious complications of these new drugs and the need for specific screening guidelines. Using data from Phase II and III randomized controlled trials, case reports, drug manufacturing data, and clinical experience, we outline the most common and serious infections associated with novel MS therapies.

Comparison of results after surgical repair of acute and chronic ulnar collateral ligament injury of the thumb.

This study sought to demonstrate that successful outcomes can be achieved with the new technique presented here for chronic ulnar collateral ligament (UCL) injury of the thumb metacarpophalangeal (MCP) joint, as well as with K-wire pinning for acute UCL injury. We followed 19 patients who suffered an UCL rupture (mean follow-up: 14.26±4.65 months) and 32 patients who presented with UCL avulsion fracture (mean follow-up: 16.81±7.54 months). We used a free tendon graft for UCL reconstruction in the UCL rupture group. Both ends of the graft were stabilized with bioabsorbable suture anchors, which were used as biotenodesis interference screws. Closed reduction and K-wire fixation was used in UCL avulsion fracture group. There were no statistically significant differences between operated and contralateral healthy thumb MCP joint in both groups in the grip strength, tip pinch strength, flexion, extension, ulnar deviation, and radial deviation movements at final follow-up. Grip strength, tip pinch strength, ulnar deviation and radial deviation were significantly better in the avulsion group than the rupture group. All patients regained full stability at the MCP joint in avulsion group; 16 patients regained full stability and 3 patients presented with mild laxity (less than 10° laxity) in rupture group. Glickel grading scale used as a functional score was excellent for 30 patients and good for 2 patients in avulsion group; it was excellent for 17 patients and good for 2 patients in rupture group. Our study shows that closed reduction and percutaneous K-wire fixation of acute displaced large UCL avulsion fracture is a simple technique and achieves adequate stability of UCL. For UCL rupture, free tendon reconstruction with bioabsorbable suture anchors provides adequate stability and stable fixation within the tunnels.

Antibody landscapes after influenza virus infection or vaccination.

We introduce the antibody landscape, a method for the quantitative analysis of antibody-mediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.

Frustrated classical Heisenberg and XY models in two dimensions with nearest-neighbor biquadratic exchange: exact solution for the ground-state phase diagram.

The ground-state phase diagram is determined exactly for the frustrated classical Heisenberg model plus nearest-neighbor biquadratic exchange interactions on a two-dimensional lattice. A square- and a rhombic-symmetry version are considered. There appear ferromagnetic, incommensurate-spiral, "up-up-down-down" (UUDD), and canted ferromagnetic states, a nonspiral coplanar state that is an ordered vortex lattice, plus a noncoplanar ordered state (a "conical vortex lattice"). In the rhombic case, which adds biquadratic terms to the Heisenberg model used widely for insulating manganites, the UUDD state found is the E-type state observed; this, along with accounting essentially for the variety of ground states observed in these materials, shows that this model probably contains the long-sought mechanism behind the UUDD state.

Thermally or magnetically induced polarization reversal in the Multiferroic CoCr2O4.

We report the unexpected evolution, with thermal and magnetic-field (H) variations, of the interrelation between the polarization P, magnetization M, and spiral wave vector Q in CoCr2O4, which has a ferrimagnetic conical-spiral magnetic order. For example, P suddenly jumps and changes its sign at the magnetic lock-in transition (T_{L}) with thermal variation, or with isothermal variation of H (without changing its direction) at T_{L}, which surprisingly occurs without change in spiral handedness (i.e., the sign of Q). The presence of multiple spiral sublattices may be behind this unusual behavior.

Matrix metalloproteinase-9 in broncho-alveolar lavage fluid of patients with non-small cell lung cancer.

AIM: To evaluate concentration of MMP-9 in blood plasma and broncho-alveolar lavage fluid (BALF) from patients with non-small cell lung cancer (NSCLC). METHODS: Blood plasma from 40 NSCLC patients and 40 healthy donors was collected and concentrations of blood plasma and BALF MMP-9 were measured using ELISA. Correlation between MMP-9 level and gender, histological type of tumor and stage of disease was analyzed. RESULTS: Levels of blood plasma MMP-9 were significantly higher in NSCLC patients (p < 0.0001) then in control group, and were especially high in patients with stage IV of disease (stage I vs stage IV - p < 0.005, stage II vs stage IV - p < 0.01, stage III vs stage IV - p < 0.01). Also, stage IV of NSCLC was characterized by the highest level of BALF MMP-9 (stage I vs stage IV - p < 0.002, stage II vs stage IV p < 0.002, and stage III vs stage IV p < 0.007). Correlation between blood plasma and BALF MMP-9 levels and gender or histological type of tumor was insignificant. CONCLUSION: Our data revealed significant correlation between tumor stage and BALF and plasma MMP-9 levels in NSCLC patients.

CIS: compound importance sampling method for protein-DNA binding site p-value estimation.

MOTIVATION: A key aspect of transcriptional regulation is the binding of transcription factors to sequence-specific binding sites that allow them to modulate the expression of nearby genes. Given models of such binding sites, one can scan regulatory regions for putative binding sites and construct a genome-wide regulatory network. In such genome-wide scans, it is crucial to control the amount of false positive predictions. Recently, several works demonstrated the benefits of modeling dependencies between positions within the binding site. Yet, computing the statistical significance of putative binding sites in this scenario remains a challenge. RESULTS: We present a general, accurate and efficient method for computing p-values of putative binding sites that is applicable to a large class of probabilistic binding site and background models. We demonstrate the accuracy of the method on synthetic and real-life data. AVAILABILITY: The procedure for scanning DNA sequences and computing the statistical significance of putative binding site scores is available upon request at http://compbio.cs.huji.ac.il/CIS/ CONTACT: nir@cs.huji.ac.il.

Non-Stoner continuum in the double exchange model.

Exact diagonalization studies of the double exchange model indicate the existence of continuum states in the single-spin-flip channel that overlap the magnons at very low energies (approximately 10(-2) eV) and extend to high energies (approximately eV). This picture differs dramatically from the prevalent view, where there are the magnons, plus the Stoner continuum at the high-energy scale, with nothing in between. The relevance of these new continuum states to inelastic neutron scattering and optical properties is discussed.

Herpesvirus-mediated systemic delivery of nerve growth factor.

Sustained systemic dissemination of therapeutic proteins from peripheral sites is an attractive prospect for gene therapy applications. Replication-defective genomic herpes simplex virus type 1 (HSV-1) vectors were evaluated for their ability to express nerve growth factor (NGF) as a model gene product both locally and systemically. Intra-articular inoculation of NGF expression vectors in rabbits resulted in significant increases in joint lavage and blood plasma NGF that persisted for 1 year. A rhesus macaque injected intra-articularly displayed a comparable increase in plasma NGF for at least 6 months, at which time the serum NGF levels of this animal were sufficient to cause differentiation of PC12 cells in culture, but not to increase footpad epidermis innervation. Long-term reporter transgene expression was observed primarily in ligaments, a finding confirmed by direct inoculation of patellar ligament. Patellar ligament inoculation with a NGF vector resulted in elevated levels of circulating NGF similar to those observed following intra-articular vector delivery. These results represent the first demonstration of sustained systemic release of a transgene product using HSV vectors, raising the prospect of new applications for HSV-1 vectors in the treatment of systemic disease.

Glimmers in the midnight zone: characterization of aligned identical residues in sequence-dissimilar proteins sharing a common fold.

Sequence comparison of proteins that adopt the same fold has revealed a large degree of sequence variation. There are many pairs of structurally similar proteins with only a very low percentage of identical residues at structurally aligned positions. It is not clear whether these few identical residues have been conserved just by coincidence, or due to their structural and/or functional role The current study focuses on characterization of STructurally Aligned Identical ResidueS (STAIRS) in a data set of protein pairs that are structurally similar but sequentially dissimilar. The conservation pattern of the residues at structurally aligned positions has been characterized within the protein families of the two pair members, and mutually highly and weakly conserved positions of STAIRS could be identified About 40% of the STAIRS are only moderately conserved, suggesting that their maintenance may have been coincidental. The mutually highly conserved STAIRS show distinct features that are associated with protein structure and function: a relatively high fraction of these STAIRS are buried within their protein structures. Glycine, cysteine, histidine, and tryptophan are significantly over-represented among the mutually conserved STAIRS. A detailed survey of these STAIRS reveals residue-specific roles in the determination of the protein's structure and function.

Physical and psychological changes with vigorous exercise in sedentary primigravidae.

PURPOSE: The present study examined the effects of exercise on physical and psychological variables in sedentary primigravidae (PRA). METHODS: A total of nine women randomly assigned to an exercise (E) (mean age = 31.3 +/- 3.1 yr) and six subjects randomly assigned to a control (C) group (mean age = 27.8 +/- 3.1 yr) fulfilled all requirements for the study. Exercise included a variety of exercise activities performed to a target heart rate of 150-156 beats x min(-1), three times per week for 15 wk. RESULTS: Results showed no significant differences between E and C groups in physical characteristics initially. A repeated measures ANOVA showed a significant group effect (P < 0.05) and a significant group by time interaction (P = 0.001) with the E group showing a significantly longer amount of time on the PWC150 test than the C group. There was no significant group, time, or group by time interaction for lactate accumulation. This occurred, despite the fact that the E group spent 56% longer on the PWC150 test and the C group spent 30% less time on the same test at the conclusion of the study. Finally, the E group in comparison to the C group showed more favorable improvements in several items related to health and well-being on the Body Cathexis Scale. There were no significant differences between E and C groups in any pregnancy outcome measures. All babies were delivered healthy at term. CONCLUSIONS: These data suggest that a vigorous exercise program can lead to significant improvements in aerobic fitness at similar lactate concentrations compared to a control group and can be well tolerated by low risk sedentary PRA without any deleterious effects occurring to herself or unborn child.

Evaluation of PSI-BLAST alignment accuracy in comparison to structural alignments.

The PSI-BLAST algorithm has been acknowledged as one of the most powerful tools for detecting remote evolutionary relationships by sequence considerations only. This has been demonstrated by its ability to recognize remote structural homologues and by the greatest coverage it enables in annotation of a complete genome. Although recognizing the correct fold of a sequence is of major importance, the accuracy of the alignment is crucial for the success of modeling one sequence by the structure of its remote homologue. Here we assess the accuracy of PSI-BLAST alignments on a stringent database of 123 structurally similar, sequence-dissimilar pairs of proteins, by comparing them to the alignments defined on a structural basis. Each protein sequence is compared to a nonredundant database of the protein sequences by PSI-BLAST. Whenever a pair member detects its pair-mate, the positions that are aligned both in the sequential and structural alignments are determined, and the alignment sensitivity is expressed as the percentage of these positions out of the structural alignment. Fifty-two sequences detected their pair-mates (for 16 pairs the success was bi-directional when either pair member was used as a query). The average percentage of correctly aligned residues per structural alignment was 43.5+/-2.2%. Other properties of the alignments were also examined, such as the sensitivity vs. specificity and the change in these parameters over consecutive iterations. Notably, there is an improvement in alignment sensitivity over consecutive iterations, reaching an average of 50.9+/-2.5% within the five iterations tested in the current study.

Bacillus weihenstephanensis sp. nov. is a new psychrotolerant species of the Bacillus cereus group.

The Bacillus cereus group comprises the four valid species Bacillus cereus, Bacillus mycoides, Bacillus thuringiensis and bacillus anthracis. Some isolates of B. cereus are known to be psychrotolerant (growth at 7 degrees C or below). Here, specific sequence differences are described between the 16S rDNA, the 23S rDNA, the 16S-23S rDNA spacer region and the genes of the major cold-shock protein homologue cspA in a variety of psychrotolerant and mesophilic B. cereus and B. mycoides strains. Randomly amplified polymorphic DNA analysis using three different primers clearly separated psychrotolerant strains of both species from the rest of the B. cereus group, as did inverse PCR patterns of the rDNA operons. These data strongly support a hitherto unrecognized fifth sub-group within the B. cereus species group comprising psychrotolerant, but not mesophilic, B. cereus strains. Despite the latter finding, the DNA sequences investigated exhibited a high degree of sequence similarity indicating a close relationship between the species of the B. cereus group. Considering the unusual importance of B. cereus in both food poisoning and food spoilage and to avoid merging all species of the group, a new species, Bacillus weihenstephanensis sp. nov., comprising psychrotolerant 'cereus' strains, is proposed. Isolates of the new species grow at 4-7 degrees C but not at 43 degrees C and can be identified rapidly using rDNA or cspA targeted PCR. The type strain is B. weihenstephanensis WSBC 10204T (= DSM 11821T).