Exploring the potential of combining transcranial magnetic stimulation and electroencephalography to investigate mild cognitive impairment and Alzheimer's disease: a systematic review.

Transcranial magnetic stimulation (TMS) and electroencephalography (EEG) are non-invasive techniques used for neuromodulation and recording brain electrical activity, respectively. The integration of TMS-EEG has emerged as a valuable tool for investigating the complex mechanisms involved in age-related disorders, such as mild cognitive impairment (MCI) and Alzheimer's disease (AD). By systematically synthesizing TMS-EEG studies, this review aims to shed light on the neurophysiological mechanisms underlying MCI and AD, while also exploring the practical applications of TMS-EEG in clinical settings. PubMed, ScienceDirect, and PsychInfo were selected as the databases for this review. The 22 eligible studies included a total of 592 individuals with MCI or AD as well as 301 cognitively normal adults. TMS-EEG assessments unveiled specific patterns of corticospinal excitability, plasticity, and brain connectivity that distinguished individuals on the AD spectrum from cognitively normal older adults. Moreover, the TMS-induced EEG features were observed to be correlated with cognitive performance and the presence of AD pathological biomarkers. The comprehensive examination of the existing studies demonstrates that the combination of TMS and EEG has yielded valuable insights into the neurophysiology of MCI and AD. This integration shows great potential for early detection, monitoring disease progression, and anticipating response to treatment. Future research is of paramount importance to delve into the potential utilization of TMS-EEG for treatment optimization in individuals with MCI and AD.

The impact of chemokine receptor CX3CR1 deficiency during respiratory infections with Mycobacterium tuberculosis or Francisella tularensis.

Recruitment of immune cells to infection sites is a critical component of the host response to pathogens. This process is facilitated partly through interactions of chemokines with cognate receptors. Here, we examine the importance of fractalkine (CX3CL1) receptor, CX3CR1, which regulates function and trafficking of macrophages and dendritic cells, in the host's ability to control respiratory infections with Mycobacterium tuberculosis or Francisella tularensis. Following low-dose aerosol challenge with M. tuberculosis, CX3CR1(-/-) mice were no more susceptible to infection than wild-type C57BL/6 mice as measured by organ burden and survival time. Similarly, following inhalation of F. tularensis, CX3CR1(-/-) mice displayed similar organ burdens to wild-type mice. CX3CR1(-/-) mice had increased recruitment of monocytes and neutrophils in the lung; however, this did not result in increased abundance of infected monocytes or neutrophils. We conclude that CX3CR1-deficiency affects immune-cell recruitment; however, loss of CX3CR1 alone does not render the host more susceptible to M. tuberculosis or F. tularensis.

Capillary basement membrane structure: a comparative study of diabetics and sexual ateliotic dwarfs.

A group of 32 sexual ateliotic dwarfs with an isolated deficiency of human growth hormone (HGH) were shown previously to resemble subjects with genetic diabetes mellitus in terms of hyperlipemia, carbohydrate intolerance, and patterns of insulin secretion. 11 of these dwarfs had needle biopsies of the quadriceps femoris carried out and tissue fixed for electron microscopy. Capillary basement membrane thickness was measured and compared with measurements previously obtained in diabetics and normal controls. Measurements were similar in controls and dwarfs (1080 +/-27 A and 1086 +/-90 A, respectively) and significantly less than in diabetics (2403 +/-119 A). Placed in juxtaposition with the absence of retinopathy in dwarfs and the high incidence in the diabetic group (41%), the data support the thesis that these anatomical abnormalities are largely independent of serum lipid and carbohydrate abnormalities. The data are consistent with a supportive, if not causative role of growth hormone in the pathogenesis of these lesions.

Repair of psoralen-treated DNA by genetic recombination in human cells infected with herpes simplex virus.

Herpes simplex virus type 1 was treated with 4,5'-8-trimethylpsoralen (psoralen) plus near-ultraviolet light in order to produce lesions (monoadducts and DNA cross-links) in the viral DNA. Human fibroblasts were infected by damaged virus under conditions in which either a single virus particle or several particles entered a given cell, and the fraction of virus-producing cells was determined. This fraction was significantly greater for multiply infected cells than for singly infected cells, indicating that the psoralen lesions are repaired more efficiently in the present of homologous, damaged DNA (multiplicity reactivation). Evidence is presented that herpes simplex virus may code for functions which participate in its own repair, both during multiplicity reactivation and during repair which occurs in singly infected cells: (a) host cells deficient in repair of lesions induced by psoralen (xeroderma pigmentosum) or the DNA cross-linking agent mitomycin C (Fanconi's anemia) exhibited normal levels of multiplicity reactivation of psoralen-treated herpes virus; (b) while xeroderma pigmentosum cells have been previously shown to be deficient in repair of psoralen-treated adenovirus under conditions of single infection, herpes virus is repaired at near normal levels in these same cells. Recombination levels between genetically marked pairs of herpes viruses were found to increase after treatment of the parental viruses with psoralen, suggesting that psoralen damage stimulates genetic recombination. This stimulation provides convincing evidence for a repair pathway in which genetic recombination between damaged viral genomes can lead to the production of viable virus.

Enhanced transformation of xeroderma pigmentosum variant cells by ultraviolet light-irradiated simian virus 40.

The role of DNA repair in transformation was investigated by infecting repair-deficient xeroderma pigmentosum (XP) variant cells, XP variant heterozygous cells, and normal human fibroblasts with simian virus 40 which had been irradiated by ultraviolet light. The transformation frequencies obtained were compared to those observed for unirradiated virus. While normal and heterozygous cells showed no differences between transformation frequencies using either irradiated or untreated virus, two XP variant cell lines were transformed 2- to 7-fold more readily with irradiated virus than with unirradiated virus. XP variant cells were also found to produce lower than normal quantities of virus following infection with either damages or undamaged virus, suggesting that increased viral production was not contributing to the increased transformation seen for these cells. Finally, the proportion of cells which repair ultraviolet light-irradiated simian virus 40 was found to be similar for wild-type and XP variant cells, suggesting that enhanced transformation in the mutant cells was not associated with a reduction in the numbers of cells which repair damaged virus. Several possible mechanisms to account for the increased transformation of XP variant cells by ultraviolet light-irradiated simian virus 40 are proposed.

In vitro differentiation of teratomas and the distribution of creatine phosphokinase and plasminogen activator in teratocarcinoma-derived cells.

Mouse teratocarcinoma cells from embryoid bodies were cultured in vitro to permit their differentiation into a number of cell types. Two enzyme activities, creatine phosphokinase (CPK) and the protease plasminogen activator, were studied to follow the developmental sequence of events in these embryoid body-derived cell cultures. CPK activity increased with time in culture, indicating the appearance of new cell types with brain- or muscle-specific enzyme activities. Plasminogen activator was detectable in extracts of embryoid bodies. This protease activity first increased and then decreased to a low level as the embryoid bodies in culture developed into differentiated cell types. These cell cultures also showed a decreased potential for tumor formation in syngeneic mice as a function of time in culture. This decrease in tumorigenic potential was correlated with the appearance of differentiated cells in vitro. Simian virus 40 (SV40) was used to infect and transform cells derived from embryoid bodies in culture. This was done to permit the establishment of cloned teratocarcinoma-derived cell lines. Twenty-nine distinct cloned permanent cell lines (called SVTER) containing the SV40-specific tumor antigen were obtained. None of these cell lines was capable of producing tumors in syngeneic mice. An analysis of the levels of creatine phosphokinase and plasminogen activator in these SVTER cell lines indicated that : (a) some cell lines had high CPK activity and little or no plasminogen activator activity, (b) some cell lines contained high levels of plasminogen activator activity with little or no CPK activity, and (c) some cell lines contained neither of these enzyme activities. No example of a cell line with high levels of both enzyme activities was observed, indicating that these two enzymes may participate in mutually exclusive developmental pathways. The SVTER cell lines may therefore be useful in reconstructing these developmental pathways in vitro.

Transformation of ultraviolet-irradiated human fibroblasts by simian virus 40 is enhanced by cellular DNA repair functions.

Human fibroblasts irradiated with ultraviolet light were either tested for survival (colony formation) or infected with simian virus 40 and examined for transformation (foci formation). For normal cell cultures, the fractions of surviving colonies which were also transformed increased with increasing irradiation dose. In contrast, little increase in the transformation of ultraviolet-irradiated repair-deficient (xeroderma pigmentosum and xeroderma pigmentosum variant) cells was observed. Similar experiments with xeroderma pigmentosum variant cells treated with caffeine following irradiation indicated that, under these conditions, the deficient cells produced more transformants among the survivors of ultraviolet irradiation than did unirradiated cells. These results suggest (1) that DNA repair functions, not DNA damage per se, are required for enhanced viral transformation in normal cells; (2) that functions involved in excision repair and functions needed for replication of ultraviolet-damaged DNA appear necessary for this stimulation; and (3) that blocking DNA replication in ultraviolet-irradiated xeroderma pigmentosum variant cells by caffeine enhances viral transformation.

Using a monoclonal antibody to identify patients with type I and type II von Willebrand's disease.

Three monoclonal antibodies produced against vWF:Ag by conventional hybridoma technique did not inhibit factor VIII coagulant activity (F. VIII:C) but did inhibit VIII ristocetin cofactor activity. The antibodies were used in an indirect competitive ELISA for quantifying von Willebrand's antigen (vWF:Ag) and compared with values obtained by the Laurell technique using commercial antibody by means of a ratio: ELISA/Laurell. For one monoclonal BD2-CC9, vWF:Ag values obtained in the two assays were in good agreement for normal and hemophilia A plasmas (normal, n = 19, ratio = 1.13 +/- .17, hemophilia A, n = 10, ratio = 0.91 +/- .15). However, type II vWD patients had a disproportionately low value of vWF:Ag with the ELISA. Use of the ratio normalized the difference among individual plasma values and allowed a significant separation of type II vWD plasma (n = 9, ratio = 0.46 +/- .19) from normal plasma (p = .0001) and type I vWD plasma (n = 8, ratio = 1.52 +/- .34) from type II vWD plasma (p = .0003) using BD2-CC9. Although the sample size was small, the greater degree of discrimination among the vWD plasmas tested with BD2-CC9 (compared with the other two antibodies [CA3-AE4, CC6-BG10]) suggests that this antibody may recognize conformational epitopes that reflect the degree of multimeric polymerization of the vWF molecule rather than simply recognize a decreased number of antigenic sites in a basic subunit. BD2-CC9 may be valuable in investigating the various types of vWD and/or the process of polymerization of this complex protein.

Revascularization for acute regional infarct: superior protection with warm blood cardioplegia.

Continuous retrograde warm blood cardioplegia was compared with two widely used hypothermic myocardial protection techniques in a canine model of acute regional myocardial ischemia with subsequent revascularization. Animals (n = 30) underwent 45 minutes of left anterior descending coronary artery occlusion then cardioplegic arrest (60 minutes), followed by separation from cardiopulmonary bypass and data collection. The cold oxygenated crystalloid cardioplegia group (CC; n = 8) and the cold blood cardioplegia group (CC; n = 10) had cardiopulmonary bypass at 28 degrees C, antegrade arrest, and intermittent retrograde delivery. The warm blood cardioplegia group (WB; n = 12) had normothermic cardiopulmonary bypass, antegrade arrest, and continuous retrograde delivery. Overall ventricular function (preload recruitable stroke work relationship; ergs x 10(3)/mL) was significantly (p < 0.001) better for WB (WB, 80 +/- 11; CB, 67 +/- 13; CC, 57 +/- 12). Systolic function (maximum elastance relationship; mm Hg/mL) was also significantly (p < 0.001) better for WB (WB, 11.6 +/- 3.6; CB, 8.6 +/- 2.7; CC, 6.2 +/- 1.3). Diastolic function (stress-strain relationship; dynes x 10(3)/cm2) revealed significantly (p < 0.001) decreased compliance for CC (WB, 20 +/- 6; CB, 19 +/- 7; CC, 27 +/- 11). Left anterior descending coronary artery regional adenosine triphosphate/adenosine diphosphate ratios were significantly (p = 0.02) worse for CC (WB, 10.2 +/- 2.3; CB, 9.4 +/- 2.6; CC, 5.6 +/- 1.5). Myocardial edema significantly (p = 0.03) increased over time only in the CC animals (WB, 0.4% +/- 2.3%; CB, -0.3% +/- 3.6%; CC, 5.5% +/- 2.3%). In this model of acute regional myocardial ischemia and revascularization, continuous retrograde warm aerobic blood cardioplegia provided superior myocardial protection compared with cold oxygenated crystalloid cardioplegia with intermediate results for cold blood cardioplegia.

Refinement of the alpha aminooleic acid bioprosthetic valve anticalcification technique.

BACKGROUND: Aminooleic acid treatment has been demonstrated to prevent porcine valve calcification and to protect valvular hemodynamic function. Initial enthusiasm was tempered by histologic studies of these AOA valves, which showed cuspal hematomas, structural loosening, and surface roughening. This prompted a systematic review of the AOA treatment process. Unsolubilized particles of alpha aminooleic acid present in the treatment solution were identified as the cause of mechanical abrasion of valve cusps during processing. These particles were eliminated with a revamped protocol, which included filtration of the AOA solution before valve preparation. METHODS: Porcine aortic valve cusps treated with this modified AOA protocol (AOA II) were studied in a rat subdermal implant model of mineralization. A juvenile sheep trial was then used to confirm the antimineralization effects of AOA II on glutaraldehyde-fixed porcine aortic roots in a circulatory model of accelerated calcification. RESULTS: Retrieved AOA II-treated cusps from the subdermal model were markedly less calcified than control cusps (AOA II, 1 +/- 0, 17 +/- 4, 23 +/- 6, and 17 +/- 10 versus control, 189 +/- 14, 251 +/- 16, 250 +/- 14, and 265 +/- 10 mg calcium/mg sample at 4, 8, 12, and 16 weeks, respectively; p < 0.0001). Morphologic examination of the AOA II cusps of the valves retrieved from the sheep demonstrated freedom from the structural loosening, surface roughening, and hematoma formation that had limited the utility of the original AOA preparation technique. Cusps from AOA II-treated porcine roots had significantly less calcium than control cusps (AOA II, 5.5 +/- 3.0 mg/g; control, 91.2 +/- 19.5 mg/g; p = 0.0004). The aortic walls had similar levels of calcification (AOA II, 156 +/- 73 mg/g; control, 159 +/- 10 mg/g; p = not significant). CONCLUSIONS: These data suggest that the modified AOA technique warrants further evaluation as an antimineralization treatment for glutaraldehyde-fixed porcine bioprostheses.

Mutagenicity of azo dyes used in foods, drugs and cosmetics before and after reduction by Clostridium species from the human intestinal tract.

Various azo dyes currently approved by the US FDA for use in foods, drugs and cosmetics are reduced by anaerobic bacteria from the human intestinal tract. These bacteria with azoreductase activities include several Clostridium species. Seven of these azo dyes and their reduction products following incubation with a Clostridium sp. were evaluated for mutagenicity in Salmonella typhimurium strains TA98 and TA100. No mutagenicity was induced in either TA98 or TA100 by any of the seven azo dyes or the reduced metabolites when tested at concentrations as high as 200 microg/plate, with or without exogenous metabolic activation by rat liver fraction S-9.

Scanning electron microscopy of post-ejaculatory spermiogenesis in the tick Ornithodoros moubata.

The final stages of spermiogenesis in ticks occur in the female genital tract. Scanning electron microscopy was used to follow the morphologic changes that occur in the sperm during this post-ejaculatory spermiogenesis in the African soft tick, Ornithodoros moubata, and to determine a time sequence for its occurrence in vivo. Characteristic features of the maturing and mature cell described include (1) differentiation and detachment of the operculum, (2) changes in cell shape corresponding to different developmental stages, (3) passive migration of the nucleus and acrosome from an anterior to a posterior position, and (4) eversion of that portion of the acrosomal canal containing the nucleus and acrosome. A possible fate for the remainder of the acrosomal canal is suggested by extrusion and detachment of spherical structures, the 'posterior bubbles', from the posterior end of the mature supermatozoon. A mechanism for cellular elongation resulting from contractions of the outer sheath is proposed.

When should nerve gaps be grafted? An experimental study in rats.

In conclusion, animal experiments have shown the following: (1) extensive elevation (mobilization) of a nerve from its bed does not interfere with its capacity to regenerate as long as the longitudinal epineural vessels are preserved, (2) suturing nerve ends under tension has a deleterious effect on the final results, (3) when a segment of nerve has been resected, the remaining nerve and the site of repair can lengthen to accommodate joint extension (within limitations), (4) if there is a segmental loss of nerve and if the nerve ends can be approximated with 10-0 epineural sutures, even if the joints must be fully flexed, the result is better than using a nerve graft, and (5) when a graft is required, it is important to avoid reversing the nerve graft. We believe direct nerve repair is preferred when flexion of the joints and mobilization of the nerve ends permits approximation with 10-0 epineural suture.

Conchal cartilage and composite grafts for correction of lower lid retraction.

Lower eyelid retraction may be due to vertical deficiency of the anterior lamella, supporting cartilage, or posterior lamella. We have used autologous cartilage grafts from the conchal bowl for reconstruction of the central lamella, reestablishing and augmenting support of the lower lid. The positioning of the graft is dependent on the specific anatomic deficiency, and the etiology of the lid retraction must be carefully evaluated. In patients with posterior lamella deficiency, the contracted lower lid retractors and conjunctiva are released and the graft is placed facing the bulbar conjunctiva and is allowed to reepithelialize. In patients in whom there is an associated skin deficiency, composite auricular grafts are used. We present our experience in 33 patients with lower lid retraction. Twenty-three patients required placement of a cartilage graft only, while 10 patients had an associated skin deficiency requiring placement of composite cartilage. In nine patients the cartilage graft was seated against the bulbar conjunctiva and allowed to reepithelialize. Reepithelialization was complete within 3 1/2 weeks in all but two of these patients. This technique has provided stable lid support in all 33 patients.

Effect of controlled local acetylsalicylic acid release on in vitro platelet adhesion to vascular grafts.

Thrombosis is the most serious acute problem for small diameter arterial bypass grafts. In this research, small diameter expanded polytetrafluoroethylene (e-PTFE) vascular grafts were coated with acetylsalicylic acid (ASA) loaded poly (d,l-lactide) (PLA) by a solvent casting method. The feasibility and efficacy of this approach were evaluated by ASA release studies and platelet adhesion tests. First, the ASA release kinetics were evaluated from the ASA/PLA coated vascular grafts in an in vitro steady flow loop model. ASA release was measured by a spectrophotometric technique. Finally, the efficacy of local ASA release to reduce in vitro canine platelet adhesion to grafts was determined with epifluorescent video microscopy and quantitative image analysis. The steady state release rates from the 5%, 10%, and 15% ASA/PLA coated grafts were 13.2 x 10(-5), 32.0 x 10(-5), and 41.5 x 10(-5) micrograms/cm2.sec, respectively. Platelet adhesion to 10% and 15% ASA/PLA coated grafts was reduced with respect to the control and 5% grafts for 10 days. Platelet adhesion to 5% ASA/PLA coated grafts was reduced with respect to controls at 2 and 10 days, but not initially.

Review of techniques used to image aortic dissection.

This article describes the imaging of aortic dissection from the perspective of a multidisciplinary imaging team. The relative merits of radiography, aortography, computed tomography, magnetic resonance imaging, ultrasound and nuclear medicine are described. Each technique has unique advantages for initial diagnosis, confirmation and follow-up. In recent years, ultrasound, computed tomography and magnetic resonance imaging have seen increased use for diagnosis of the condition.