Total Disruptions Research Articles

Mechanism of the Synergistic Toxicity of Ampicillin and Cefazoline on Selenastrum capricornutum.

Ampicillin (AMP) and cefazolin (CZO) are commonly used β-lactam antibiotics which are extensively globally produced. Additionally, AMP and CZO are known to have relatively high ecotoxicity. Notably, the mix of AMP and CZO creates a synergistic effect that is more harmful to the environment, and how exposure to AMP-CZO can induce synergism in algae remains virtually unknown. To yield comprehensive mechanistic insights into chemical toxicity, including dose-response relationships and variations in species sensitivity, the integration of multiple endpoints with de novo transcriptomics analyses were used in this study. We employed Selenastrum capricornutum to investigate its toxicological responses to AMP and CZO at various biological levels, with the aim of elucidating the underlying mechanisms. Our assessment of multiple endpoints revealed a significant growth inhibition in response to AMP at the relevant concentrations. This inhibition was associated with increased levels of reactive oxygen species (ROS) and perturbations in nitrogen metabolism, carbohydrate metabolism, and energy metabolism. Growth inhibition in the presence of CZO and the AMP-CZO combination was linked to reduced viability levels, elevated ROS production, decreased total soluble protein content, inhibited photosynthesis, and disruptions in the key signaling pathways related to starch and sucrose metabolism, ribosome function, amino acid biosynthesis, and the production of secondary metabolites. It was concluded from the physiological level that the synergistic effect of Chlorophyll a (Chla) and Superoxide dismutase (SOD) activity strengthened the growth inhibition of S. capricornutum in the AMP-CZO synergistic group. According to the results of transcriptomic analysis, the simultaneous down-regulation of LHCA4, LHCA1, LHCA5, and sodA destroyed the functions of the photosynthetic system and the antioxidant system, respectively. Such information is invaluable for environmental risk assessments. The results provided critical knowledge for a better understanding of the potential ecological impacts of these antibiotics on non-target organisms.

Application of broken windows theory to identify flow disruptions in neurosurgery procedure.

Addressing flow disruptions (FDs) in neurosurgery requires a multifaceted approach. Strategies like improved communication protocols, minimizing interruptions, improving coordination among team, optimizing operating room layout, and promoting user-centered design can help mitigate the challenges and enhance the overall flow and safety of neurosurgical procedures. Thirty neurosurgery cases were observed at two tertiary care facilities. The data collected were from wheels into the operating room to wheels out from the operating room. Data points were categorized using a human factors taxonomy known as RIPCHORD-TWA (Realizing Improved Patient Care Through Human-Centered Operating Room Design for Threat Window Analysis). Of the 541 total disruptions observed, coordination issues were the most prevalent (26.25%), followed by layout issues (26.06%), issues related to interruption (22.55%), communication (22.37%), equipment issues (2.40%) and usability issues (0.37%) comprised the remainder of the observations. This translated into one disruption every 2.7 min. Instead of focusing exclusively on errors and adverse events, we propose conceptualizing the accumulation of disruptions as "threat windows" to analyze potential threats to the integrity of the care system. This perspective allows for the improved identification of system weaknesses or threats, affording us the ability to address these inefficiencies and intervene before errors and adverse events may occur.

Partial stellar tidal disruption events and their rates

ABSTRACT Tidal disruption events (TDEs) of stars operated by massive black holes (MBHs) will be detected in thousands by upcoming facilities such as the Vera Rubin Observatory. In this work, we assess the rates of standard total TDEs, destroying the entire star, and partial TDEs, in which a stellar remnant survives the interaction, by solving 1D Fokker–Planck equations. Our rate estimates are based on a novel definition of the loss cone whose size is commensurate with the largest radius at which partial disruptions can occur, as motivated by relativistic hydrodynamical simulations. Our novel approach unveils two important results. First, partial TDEs can be more abundant than total disruptions by a factor of a few to a few tens. Second, the rates of complete stellar disruptions can be overestimated by a factor of a few to a few tens if one neglects partial TDEs, as we find that many of the events classified as total disruptions in the standard framework are in fact partial TDEs. Accounting for partial TDEs is particularly relevant for galaxies harbouring a nuclear stellar cluster featuring many events coming from the empty loss cone. Based on these findings, we stress that partial disruptions should be considered when constraining the luminosity function of TDE flares; accounting for this may reconcile the theoretically estimated TDE rates with the observed ones.

Interfering with Protein Z Dependent Inhibition of Factor Xa Improves Coagulation in Hemophilia

Blood coagulation involves a highly regulated balance between pro-coagulant and anticoagulant activities, allowing for the abatement of bleeding while limiting clot formation, which, if unchecked, could result in thrombosis. Hemostasis is triggered upon vascular injury when extravascular tissue factor (TF) binds plasma coagulation factor VIIa (FVIIa) forming a FVIIa/TF complex that generates limited amounts of activated factors IX (FIXa) and X (FXa). In normal hemostasis, FIXa with FVIIIa dramatically amplifies the production of FXa; FXa with FVa cleaves prothrombin to thrombin, and thrombin cleaves fibrinogen to form a fibrin clot. FXa generated by FVIIa/TF alone is insufficient for normal coagulation as FVIIa/TF activity is limited due to tissue factor pathway inhibitor (TFPI) and TFPI and other plasma protease inhibitors suppress the action of the initially generated FXa (and thrombin). Lacking FVIII or FIX, hemophiliacs fail to generate the additional FXa that is critical for normal hemostasis. Several methods designed to reduce the activity of endogenous inhibitors of coagulation are currently being investigated as a means to ameliorate the bleeding in hemophilia. These include antibody-mediated reduction in the activities of TFPI and protein S, and siRNA-mediated reduction in antithrombin (AT).Protein Z (PZ) is a vitamin K-dependent coagulation factor that serves as the cofactor for FXa inhibition by the serpin, PZ-dependent protease inhibitor (ZPI), at phospholipid surfaces. If inhibition of the action of PZ/ZPI significantly enhanced coagulation in hemophilia, it might be associated with a reduced risk of thrombosis than other approaches. In the latter regard it is of interest that TFPI, PS and AT deficiency are associated with clinical thrombotic disease and mice lacking these proteins die in utero or perinatally of thromboembolic disease. In contrast, PZ and ZPI KO mice appear healthy.Re-bleeding is a hallmark of clinical hemophilia. A tail vein re-bleeding (TVRB) assay, adapted from the saphenous vein re-bleeding assay of Whinna, was developed to assess the effects of PZ and ZPI deficiency on re-bleeding in the hemophilia A mouse model. In this assay, the lateral vein of the tail (diameter 2.25 mm) of an anesthetized mouse is lacerated to a depth of 1 mm with scalpel and the tail placed in warm saline. When bleeding stops, the wound is wiped with a balled Kimwipe to re-induce bleeding and the tail replaced in warm saline. This process is repeated and the number of wound disruptions occurring within 15 minutes is recorded. In normal mice, the period of bleeding following each wound disruption remains relatively constant, whereas in hemophilia mice the bleeding periods tend to progressively prolong with each subsequent disruption leading to a reduced number of total disruptions over 15 minutes.Disruptions in the mouse TVRB assay were: for C57Bl/6 25.8+1.7 (mean+SEM); for FVIII KO 4.2+1.3; for PZ/FVIII double KOs 15.2+3.2; for ZPI/FVIII doubles KOs 14.6+3.5; for WT/KO littermates 4.0+2.6; and for FVIII KO with 100% human FVIII replacement 25.4+3.7. Based on FVIII dose-response experiments, the results in PZ/FVIII and ZPI/FVIII double KOs were equivalent to ~15% FVIII replacement. This outcome of the TVRB assays was confirmed in tests of the survival of sibling WT/FVIII KO (0%, n=5) and ZPI/FVIII double KO (75%, n=12) mice following tail transection 10 mm from the tip.To assess the translation of the PZ/ZPI results in mice to humans, the effect of an anti-PZ monoclonal antibody (Mab) was compared to FVIII replacement on TF (1 pM) induced thrombin generation in human hemophilia A plasma. The Mab enhanced thrombin generation in hemophilia plasma to a similar degree as ~15% FVIII.These studies provide proof of concept, both in vivo in mice and in vitro in human plasma, that blockade of the PZ/ZPI system may be sufficient to alter the phenotype of severe hemophilia to that of mild hemophilia, perhaps with limited thrombotic risk. DisclosuresNo relevant conflicts of interest to declare.

Impact of COVID-19 on adolescent and emerging adult brain tumor survivors and their parents.

BackgroundThe COVID‐19 pandemic has prompted unprecedented challenges, contributing to greater difficulties among families of children with special health care needs, such as pediatric brain tumor survivors. We examined the impact of the pandemic on psychosocial functioning of adolescent and emerging adult survivors and their parents. We hypothesized that COVID‐19 disruptions and survivor social connectedness would be associated with survivor‐reported posttraumatic stress and family outcomes, including family functioning, parenting, and parent mental health.ProcedureFifty‐five families (44 survivors, 48 parents) were recruited via phone and email to participate in the study. Survivors were ages 13–25 (M = 19.62, SD = 3.47) and at least 5 years post diagnosis. Parents completed the COVID‐19 Exposure and Family Impact Survey (CEFIS), and survivors completed the Environmental influences on Child Health Outcomes (ECHO) COVID‐19 child self‐report form, which assessed pandemic impacts on their psychosocial functioning.ResultsParents reported a mean of 7.52 (SD = 2.83) disruptions to their families’ lives. The pandemic negatively affected survivors’ life satisfaction (M diff = 0.46, t(44) = 3.96, p < .001), with 92% reporting reduced social connectedness (n = 39). Total disruptions due to COVID‐19 and survivor social connectedness predicted survivor‐reported posttraumatic stress, above and beyond survivors’ pre‐pandemic psychosocial risk. Most parents reported positive changes in their parenting (n = 31, 67.4%) and family cohesion (n = 30, 66.7%). However, they also reported worsened mood (n = 28, 62.3%) and increased anxiety (n = 31, 71.1%).ConclusionsParents and survivors reported positive and negative impacts of COVID‐19, which had downstream consequences on survivor psychosocial functioning. Follow‐up care should consider potential adverse effects on social connectedness and stress symptoms.

Tidal Disruptions of Main-sequence Stars. I. Observable Quantities and Their Dependence on Stellar and Black Hole Mass

Abstract This paper introduces a series of papers presenting a quantitative theory for the tidal disruption of main-sequence stars by supermassive black holes. Using fully general relativistic hydrodynamics simulations and MESA-model initial conditions, we explore the pericenter-dependence of tidal disruption properties for eight stellar masses ( ) and six black hole masses ( ). We present here the results most relevant to observations. The effects of internal stellar structure and relativity decouple for both the disruption cross section and the characteristic energy width of the debris. Moreover, the full disruption cross section is almost independent of M ⋆ for M ⋆/M ⊙ ≲ 3. Independent of M ⋆, relativistic effects increase the critical pericenter distance for full disruption events by up to a factor of ∼3 relative to the Newtonian prediction. The probability of a direct capture is also independent of M ⋆; at M BH/M ⊙ ≃ 5 × 106 this probability is equal to the probability of a complete disruption. The breadth of the debris energy distribution ΔE can differ from the standard estimate by factors of 0.35 − 2, depending on M ⋆ and M BH, implying a corresponding change (∝(ΔE)−3/2) in the characteristic mass-return timescale. We provide analytic forms, suitable for use in both event rate estimates and parameter inference, to describe all these trends. For partial disruptions, we find a nearly universal relation between the star’s angular momentum and the fraction of M ⋆ remaining. Within the “empty loss-cone” regime, partial disruptions must precede full disruptions. These partial disruptions can drastically affect the rate and appearance of subsequent total disruptions.

Tidal Disruptions of Main-sequence Stars. V. The Varieties of Disruptions

Abstract Tidal disruption events (TDEs) are generally imagined as the complete disruption of a star when it passes close to a supermassive black hole (SMBH). Relativistic apsidal precession is thought to quickly “circularize” the bound debris, forming a compact accretion disk, which then emits a flare of standardized light curve and spectrum. We show here that this picture holds in only a minority of cases. TDEs are more diverse and can be grouped into several categories distinguished by stellar pericenter distance r p ; we estimate the relative frequency of these categories. Rapid circularization is rare both because it requires ( ) and because most events with lead to direct capture. For larger pericenter distances, (for M BH = 106 M ⊙), main-sequence stars with M * ≲ 3 are completely disrupted, but the bound debris orbits are highly eccentric and possess semimajor axes ∼100× the scale of the expected compact disk. Partial disruptions with fractional mass loss ≳10% occur with a rate similar to that of total disruptions; for fractional mass loss ≳50%, the rate is ≈1/3 as large. Partial disruptions—which must precede total disruptions when the stars’ angular momenta evolve in the “empty loss-cone” regime—change the orbital energy by factors ≳O(1). Partial disruption remnants are in general far from thermal equilibrium. Depending on its orbital energy and conditions within the stellar cluster surrounding the SMBH, a remnant may return after ∼O(100)–O(1000) yr and be fully disrupted, or it may rejoin the stellar cluster.

Freezing of Gait in People with Parkinson's Disease: Nature, Occurrence, and Risk Factors.

Freezing of gait (FOG) is a common symptom of Parkinson's disease (PD) which can result in falls and fall related injuries, poor quality of life and reduced functional independence. It is a heterogeneous phenomenon that is difficult to quantify and eludes a unified pathophysiological framework. Our aim was to document the occurrence and nature of freezing, cognitive stops and stumbles in people with PD during walks with varying cognitive loads and conditions designed to elicit FOG. 130 people with PD walked under four conditions (normal walking, walking plus easy and hard dual-tasks, and a FOG elicitation condition. Video and accelerometry recordings were examined to document freezes and other gait disruptions. Participants experienced 391 freezes, 97 cognitive stops and 73 stumbles in the trial walks; with total gait disruptions increasing with task complexity. Most freezes in the FOG elicitation condition occurred during turning and approach destination. People who experienced freezing during the walks were more likely to have Postural Instability and Gait Difficulty (PIGD) subtype, longer disease duration and more severe UPDRS part II and part III sub-scores than people who did not freeze. They also took higher doses of levodopa, reported freezing in the past month, more prior falls, had poorer executive function, poorer proprioception, slower reaction time, poorer standing and leaning balance, more depressive symptoms, lower quality of life and greater fear of falling. PD disease duration, reduced controlled leaning balance and poor proprioception were identified as independent and significant determinants of freezing in logistic regression analysis. The multiple motor and cognitive factors identified as being associated with freezing, including poor proprioception and impaired controlled leaning balance provide new insights into this debilitating PD symptom and may contribute to potential new targets for rehabilitation.

Evaluating the Magnitude and Spatial Extent of Disruptions Across Interdependent National Infrastructure Networks

Abstract Critical infrastructure networks are geographically distributed systems spanning multiple scales. These networks are increasingly interdependent for normal operations, which causes localized asset failures from natural hazards or man-made interference to propagate across multiple networks, affecting those far removed from an initiating failure event. This paper provides methodology to identify such failure propagation effects by quantifying the spatial variability in magnitude, frequency, and disruptive reach of failures across national infrastructure networks. To achieve this, we present methodology to combine functionally interdependent infrastructure networks with geographic interdependencies by simulating complete asset failures across a national scale grid of spatially localized hazards. A range of metrics are introduced to compare the systemic vulnerabilities of infrastructure systems and the resulting spatial variability in both the potential for initiating widespread failures and the risk of being impacted by distant hazards. We demonstrate the approach through an application in New Zealand of infrastructures across the energy (electricity, petroleum supply), water and waste (water supply, wastewater, solid waste), telecommunications (mobile networks), and transportation sectors (passenger rail, ferry, air, and state highways). In addition to identifying nationally significant systemic vulnerabilities, we observe that nearly half (46%) of the total disruptions across the simulation set can be attributed to network propagation initiated asset failures. This highlights the importance in considering interdependencies when assessing infrastructure risks and prioritizing investment decisions for enhancing resilience of national networks.

Finger reconstruction in children by the transfer of hand segments

Aim. We aimed to evaluate the possibility of reconstruction of amputated fingers using various methods of hand segment transfer in children.&#x0D; Materials and methods. A retrospective analysis of the reconstruction of the first and triphalangeal fingers of an injured hand using a segment transfer method in 31 children was performed. Eleven patients had a mechanical injury; 12, a gunshot injury; 7, a burn injury; and 1, a freezing injury. The reconstruction of 32 fingers was performed by the transfer of an intact triphalangeal finger (3), defective finger (3), finger stump (14), and a metacarpal (12). The surgery was performed using traditional (16) and original (16) methods. In 26 cases, skin grafting using donor resources from remote areas was required for segment transfer. Newly developed approaches enable the transfer of the defective finger and any stump of the main finger phalanges and metacarpals, irrespective of their location, amputation level, hand defect character, level of cicatrical changes of the soft tissues, and impaired circulation, while adequately preventing ischemic complications.&#x0D; Results. Survival of all the transferred segments, including those with total cicatrical tissue changes and vascular disruptions, was achieved. The analysis of results showed that handgrip was restored in 31 hands. The best results were achieved in the transfer of intact fingers. Transfer of the utile segments enabled the reconstruction of the double-sided grip with minimum donor retrieval. Two-point discrimination was 2 mm for finger transfer, 4.5 mm for finger stump, and 6.5–7.4 mm for the metacarpal stump.&#x0D; Conclusion. The transfer of injured hand segments in children for finger reconstruction provides acceptable functional and anatomical results. This method can be used in combination with other finger reconstruction methods. Advanced technical and tactical approaches have widened the criteria of segment suitability and indications for the use of this method.

Using Broken Windows Theory as the Backdrop for a Proactive Approach to Threat Identification in Health Care.

Historically, health care has relied on error management techniques to measure and reduce the occurrence of adverse events. This study proposes an alternative approach for identifying and analyzing hazardous events. Whereas previous research has concentrated on investigating individual flow disruptions, we maintain the industry should focus on threat windows, or the accumulation of these disruptions. This methodology, driven by the broken windows theory, allows us to identify process inefficiencies before they manifest and open the door for the occurrence of errors and adverse events. Medical human factors researchers observed disruptions during 34 trauma cases at a Level II trauma center. Data were collected during resuscitation and imaging and were classified using a human factors taxonomy: Realizing Improved Patient Care Through Human-Centered Operating Room Design for Threat Window Analysis (RIPCHORD-TWA). Of the 576 total disruptions observed, communication issues were the most prevalent (28%), followed by interruptions and coordination issues (24% each). Issues related to layout (16%), usability (5%), and equipment (2%) comprised the remainder of the observations. Disruptions involving communication issues were more prevalent during resuscitation, whereas coordination problems were observed more frequently during imaging. Rather than solely investigating errors and adverse events, we propose conceptualizing the accumulation of disruptions in terms of threat windows as a means to analyze potential threats to the integrity of the trauma care system. This approach allows for the improved identification of system weaknesses or threats, affording us the ability to address these inefficiencies and intervene before errors and adverse events may occur.

Comprehensive splicing functional analysis of DNA variants of the BRCA2 gene by hybrid minigenes

IntroductionThe underlying pathogenic mechanism of a large fraction of DNA variants of disease-causing genes is the disruption of the splicing process. We aimed to investigate the effect on splicing of the BRCA2 variants c.8488-1G > A (exon 20) and c.9026_9030del (exon 23), as well as 41 BRCA2 variants reported in the Breast Cancer Information Core (BIC) mutation database.MethodsDNA variants were analyzed with the splicing prediction programs NNSPLICE and Human Splicing Finder. Functional analyses of candidate variants were performed by lymphocyte RT-PCR and/or hybrid minigene assays. Forty-one BIC variants of exons 19, 20, 23 and 24 were bioinformatically selected and generated by PCR-mutagenesis of the wild type minigenes.ResultsLymphocyte RT-PCR of c.8488-1G > A showed intron 19 retention and a 12-nucleotide deletion in exon 20, whereas c.9026_9030del did not show any splicing anomaly. Minigene analysis of c.8488-1G > A displayed the aforementioned aberrant isoforms but also exon 20 skipping. We further evaluated the splicing outcomes of 41 variants of four BRCA2 exons by minigene analysis. Eighteen variants presented splicing aberrations. Most variants (78.9%) disrupted the natural splice sites, whereas four altered putative enhancers/silencers and had a weak effect. Fluorescent RT-PCR of minigenes accurately detected 14 RNA isoforms generated by cryptic site usage, exon skipping and intron retention events. Fourteen variants showed total splicing disruptions and were predicted to truncate or eliminate essential domains of BRCA2.ConclusionsA relevant proportion of BRCA2 variants are correlated with splicing disruptions, indicating that RNA analysis is a valuable tool to assess the pathogenicity of a particular DNA change. The minigene system is a straightforward and robust approach to detect variants with an impact on splicing and contributes to a better knowledge of this gene expression step.

Development and Pilot Evaluation of a Preoperative Briefing Protocol for Cardiovascular Surgery

Preprocedural briefings have been adopted in many high consequence environments, but have not been widely accepted in medicine. We sought to develop, implement, and evaluate a preoperative briefing for cardiovascular surgery. The briefing was developed by using a combined questionnaire and semistructured focus group approach involving five subspecialties of surgical staff (n=55). The results were used to design and implement a preoperative briefing protocol. The briefing was evaluated by monitoring surgical flow disruptions, circulating nurse trips to the core, time spent in the core, and cost-waste reports before and after implementation of the briefing across 16 cardiac surgery cases. Focus group data indicated consensus among surgical staff concerning briefing benefits, duration, location, content, and potential barriers. Disagreement arose concerning timing of the brief and the roles of key participants. After implementation of the briefing, there was a reduction in total surgical flow disruptions per case (5.4 preimplementation versus 2.8 postimplementation, p=0.004) and reductions in per case average of procedural knowledge disruptions (4.1 versus 2.17, p=0.004) and miscommunication events (2.5 versus 1.17, p=0.03). There was no significant reduction in disruptions because of equipment preparation or disruptions from patient-related issues. On average, briefed teams experienced fewer trips to the core (10 versus 4.7, p=0.004) and spent less time in the core (397.4 seconds versus 172.3 seconds, p=0.006), and there was a trend toward decreased waste (30% versus 17%, p=0.15). These findings demonstrate the feasibility of creating a specialty-specific preoperative briefing to decrease surgical flow disruptions and improve patient safety in the operating room.

Ligamentoplasty of the forearm interosseous membrane using the semitendinosus tendon: anatomical study and surgical procedure

Total longitudinal disruptions of the interosseous membrane can allow proximal radius migration and are seen in Essex-Lopresti lesions. We propose an original technique of ligamentoplasty using the semitendinosus tendon. The graft corresponds to the forearm rotation axis for an optimized isometry and longitudinal stabilization. Our ligamentoplasty technique was performed on ten fresh frozen right forearms. We successively assessed the innocuousness, efficiency and resistance of the ligamentoplasty. The ligamentoplasty induced neither passive limitation of pronation-supination nor neurovascular lesions. It prevented from radius proximal migration. The mean load to failure was 28 kg at both ulnar and radial sides of the graft. Our technique is original for the type and position of the graft. It seems safe, efficient and resistant enough for in vivo procedures. This technique decreases longitudinal loads on the radius. It should be indicated in patients with Essex-Lopresti syndrome, in association with radial head internal fixation or arthroplasty.

Nonoxynol-9 100 mg gel

To evaluate the safety of 100 mg nonoxynol-9 (N-9) gel, a vaginal microbicide, on the genital mucosa of women from Malawi and Zimbabwe in preparation for a phase III efficacy study. HIV-uninfected women (180) were enrolled and randomized to either N-9 or placebo gel and instructed to insert gel into the vagina twice daily for 14 days. Follow up examinations were conducted at 7 and 14 days. The number of adverse events in the N-9 gel group was higher than in the placebo group (40% versus 13%; P < 0.01). Reported number of any genital symptoms was significantly higher in the N-9 group (38% N-9, 13% placebo; P = 0.01). The number of total epithelial disruptions was higher in the N-9 group (20% versus 3%; P < 0.01); however, the number of genital ulcers and abrasions in the N-9 group was low (2% and 3%, respectively) and not different from that in the placebo group (1% and 2%, respectively). N-9 gel 100 mg caused a significant increase in the rate of genital symptoms and epithelial disruptions compared with placebo. The clinical significance of these epithelial disruptions is unknown. Although these findings alone were not sufficient to cancel the planned phase III study, when considered together with the negative results from the COL-1492 effectiveness trial of 52.5 mg N-9 gel, the decision was made to cancel the planned phase III trial of 100 mg N-9 gel.

Total vaginal cuff disruptions associated with total laparoscopic hysterectomy for endometriosis

Total vaginal cuff disruptions associated with total laparoscopic hysterectomy for endometriosis

MHP1, an essential gene in Saccharomyces cerevisiae required for microtubule function.

The gene for a microtubule-associated protein (MAP), termed MHP1 (MAP-Homologous Protein 1), was isolated from Saccharomyces cerevisiae by expression cloning using antibodies specific for the Drosophila 205K MAP. MHP1 encodes an essential protein of 1,398 amino acids that contains near its COOH-terminal end a sequence homologous to the microtubule-binding domain of MAP2, MAP4, and tau. While total disruptions are lethal, NH2-terminal deletion mutations of MHP1 are viable, and the expression of the COOH-terminal two-thirds of the protein is sufficient for vegetative growth. Nonviable deletion-disruption mutations of MHP1 can be partially complemented by the expression of the Drosophila 205K MAP. Mhp1p binds to microtubules in vitro, and it is the COOH-terminal region containing the tau-homologous motif that mediates microtubule binding. Antibodies directed against a COOH-terminal peptide of Mhp1p decorate cytoplasmic microtubules and mitotic spindles as revealed by immunofluorescence microscopy. The overexpression of an NH2-terminal deletion mutation of MHP1 results in an accumulation of large-budded cells with short spindles and disturbed nuclear migration. In asynchronously growing cells that overexpress MHP1 from a multicopy plasmid, the length and number of cytoplasmic microtubules is increased and the proportion of mitotic cells is decreased, while haploid cells in which the expression of MHP1 has been silenced exhibit few microtubules. These results suggest that MHP1 is essential for the formation and/or stabilization of microtubules.

Cheyne-Stokes Respiration Presenting as Sleep Apnea Syndrome: Clinical and Polysomnographic Features

This study reports polysomnographic features of five patients with Cheyne-Stokes respiration (CSR). They were referred for evaluation of presumptive sleep apnea syndrome on the basis of history and physical examination, but were found to have predominantly CSR on all-night sleep study. On the initial polysomnographic study, CSR comprised 47 to 86% of all disordered-breathing events. Cheyne-Stokes respiration resulted in considerable oxyhemoglobin desaturation (mean baseline saturation was 95 +/- 4 +/- SD, and lowest saturation was 76 +/- 8). More than one-half of all CSR events resulted in awakenings or arousals. Evidence of upper airway obstruction was noted in the majority of CSR events in three of five patients. Four patients were treated with theophylline; one who refused drug therapy was treated with nasal continuous positive airway pressure (CPAP). Comparison of sleep studies before and after therapy showed a significant decrease in the CSR index (29 +/- 11 versus 2 +/- 2) and in the maximal oxyhemoglobin desaturation associated with CSR (13 +/- 5 versus 3 +/- 2), and an improvement in lowest O2 saturation associated with CSR (76 +/- 8 versus 91 +/- 4). Total disruptions in sleep architecture per hour of sleep improved significantly with therapy (46 +/- 21 versus 20 +/- 8). We conclude that the clinical presentation of CSR can be indistinguishable from that of the "traditional" sleep apnea hypopnea syndrome and can result in major oxyhemoglobin desaturation and sleep fragmentation. Theophylline results in considerable improvement in the disordered breathing of CSR during sleep.

Total disruption of surgical wounds of the abdominal wall with reference to plasma proteinemia and plasma ascorbic acid

1. 1. An analysis of seven total disruptions of abdominal incisions is presented. 2. 2. The presence of hypoproteinemia and of deficiency of plasma ascorbic acid in these cases and the possible influence of these factors is discussed.