Label-free screening of single biomolecules through resistive pulse sensing technology for precision medicine applications.

Employing integrated nano- and microfluidic circuits for detecting and characterizing biological compounds through resistive pulse sensing technology is a vibrant area of research at the interface of biotechnology and nanotechnology. Resistive pulse sensing platforms can be customized to study virtually any particle of choice which can be threaded through a fluidic channel and enable label-free single-particle interrogation with the primary read-out signal being an electric current fingerprint. The ability to perform label-free molecular screening with single-molecule and even single binding site resolution makes resistive pulse sensing technology a powerful tool for analyzing the smallest units of biological systems and how they interact with each other on a molecular level. This task is at the core of experimental systems biology and in particular 'omics research which in combination with next-generation DNA-sequencing and next-generation drug discovery and design forms the foundation of a novel disruptive medical paradigm commonly referred to as personalized medicine or precision medicine. DNA-sequencing has approached the 1000-Dollar-Genome milestone allowing for decoding a complete human genome with unmatched speed and at low cost. Increased sequencing efficiency yields massive amounts of genomic data. Analyzing this data in combination with medical and biometric health data eventually enables understanding the pathways from individual genes to physiological functions. Access to this information triggers fundamental questions for doctors and patients alike: what are the chances of an outbreak for a specific disease? Can individual risks be managed and if so how? Which drugs are available and how should they be applied? Could a new drug be tailored to an individual's genetic predisposition fast and in an affordable way? In order to provide answers and real-life value to patients, the rapid evolvement of novel computing approaches for analyzing big data in systems genomics has to be accompanied by an equally strong effort to develop next-generation DNA-sequencing and next-generation drug screening and design platforms. In that context lab-on-a-chip devices utilizing nanopore- and nanochannel based resistive pulse-sensing technology for DNA-sequencing and protein screening applications occupy a key role. This paper describes the status quo of resistive pulse sensing technology for these two application areas with a special focus on current technology trends and challenges ahead.

[Avulsion of the inferior rectus muscle due to a dog-bite and reconstruction of its function]. / Durchtrennung des Musculus rectus inferior durch Hundebiss und Rekonstruktion der Muskelfunktion - eine Kasuistik.

BACKGROUND: Injuries of an extraocular muscle or of the globe due to a dog-bite are rare. PATIENT: An 43-year-old patient presented with an orbital dog bite. He had a complete avulsion of the inferior rectus muscle. During the primary surgical repair, the proximal part of the muscle could not be found. The distal part of the inferior rectus muscle was sutured to the tissue in the original region of the retracted inferior rectus muscle. After surgical repair the patient could read without complaint. We explain the unexpected remarkable postoperative result on the basis of high resolution MRI: Although the muscle belly was lost, some parts of the muscle sheath forming connections to Tenon's capsule had remained. These allowed a certain function of the muscle. CONCLUSIONS: If during the primary surgical repair of a traumatic avulsion of an extraocular muscle the proximal part of the muscle could not be found, it is worth to suture the distal part of the muscle to tissues (empty muscle sheath, connections to Tenon's capsule) in the original region of the lost muscle. This prevents a further retraction of the proximal part of the muscle and helps the finding and differentiation of the structures of the muscle during a prospectivly following surgical repair.

T-cut in the bottom of the scleral pocket in combined cataract and glaucoma surgery.

PURPOSE: To determine whether radial transsection of the inner lamina of the phaco tunnel (T-cut) allows intraocular pressure (IOP) control in cases of co-existing cataract and glaucoma and to evaluate the results of this glaucoma triple procedure. SETTING: Department of Ophthalmology, Hanusch Hospital, Vienna, Austria. METHODS: In a prospective study, a T-shaped incision in the tunnel floor was performed in 43 eyes (Group A); 48 eyes (Group B) had phacotrabeculectomy (phacoemulsification and trabeculectomy of a 3.0 x 2.0 mm tissue block). RESULTS: At the end of a minimum follow-up of 24 months in Group A (range 24 to 30 months) and of 28 months in Group B (range 28 to 44 months), there was no significant difference in the extent of IOP reduction between groups. Intraocular pressure was well controlled (< or =20 mm Hg) without antiglaucoma therapy in 27 eyes (62.8%) in Group A and 30 (62.5%) in Group B. Eleven eyes (25.6%) in Group A and 14 (29.2%) in Group B achieved an IOP of 20 mm Hg or less with antiglaucoma therapy. Five eyes (11.6%) in Group A and 4 (8.3%) in Group B required surgical revision. Complications included hypotony (Group A, 5 eyes; Group B, 3 eyes), hyphema (Group A, 8 eyes; Group B, 6 eyes), malignant glaucoma (Group B, 1 eye), in-the-bag hematoma (Group B, 1 eye), and fibrin exudation (Group B, 1 eye). CONCLUSION: Phacoemulsification with a T-cut in the tunnel floor was a safe and effective combined procedure and, in this regard, equivalent to phacotrabeculectomy.

Effects of growth hormone on insulin-like growth factors and binding proteins before and after renal transplantation.

Three short children with severe chronic renal failure were treated with recombinant human growth hormone (rhGH) for 2 years. Each received a transplant in the 2nd year. Serum collected before and during rhGH therapy was analysed retrospectively by Western ligand blot and immunoblotting techniques. In addition, radioimmuno-assays for insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), acid-labile subunit (ALS) and IGFBP-1 were performed. IGFBPs in serum, detected by Western ligand blot, were identified as IGFBP-3, -2, -1 and -4 by immunoblot. The serum concentration of IGF-I in each child rose approximately fourfold with rhGH before transplantation and subsequently remained elevated. IGFBP-3 levels rose to double the pretreatment value, but dropped to normal levels following transplantation, while ALS rose with rhGH treatment and remained increased after transplantation. IGFBP-1 levels changed little with rhGH but fell following transplantation. A low molecular weight form of IGFBP-3 was noted at 30 kilodaltons on immunoblot which was not clearly seen on the ligand blot. IGFBP-2 was present as a distinct band on Western ligand blot before transplantation and appeared decreased in intensity subsequently. IGFBP-1, seen on immunoblot clearly before transplant, disappeared after the transplant. rhGH successfully improved growth in these children, in association with a fourfold increase in IGF-I levels, which was maintained following transplantation. The reduction in IGFBPs following transplantation suggests correction of impaired clearance by the diseased kidney.

Immunization of mice with Salmonella typhimurium C5 aroA expressing a genetically toxoided derivative of the pneumococcal toxin pneumolysin.

An attenuated Salmonella strain expressing a genetically toxoided derivative of the pneumococcal toxin pneumolysin was constructed by first transforming a methylation-positive, restriction-negative Salmonella with plasmid pJCP20M, a derivative of pBR322 containing the modified pneumolysin gene. Plasmid DNA was then extracted and transformed into Salmonella typhimurium C5 aroA. The transformant (denoted JM8) was capable of constitutively expressing the modified pneumolysin gene in vitro and stably maintained the recombinant plasmid containing the pneumococcal DNA, even in the absence of antibiotic selection. When JM8, or the parental Salmonella C5 aroA carrying pBR322 (denoted JM6), were administered orally to mice, both strains were capable of at least transient colonization of the Peyer's patches. Sera from JM8 mice (but not those fed JM6) had significant anti-pneumolysin IgG and IgA ELISA titres. Intraperitoneal administration of JM8 resulted in higher anti-pneumolysin IgG titres, but lower specific IgA levels.

Effects of metaphit on phencyclidine and serotonin2 receptors.

We have investigated whether metaphit, a derivative of phencyclidine (PCP) which irreversibly binds to a population of PCP receptor sites in rat brain, blocks PCP-induced head-twitch response which is produced through serotonin2 (5-HT2) receptors, and also whether metaphit decreases the capacity of 5-HT2 receptors. Metaphit (1 mumol/rat) had decreased the intensity of PCP-induced head-twitch response and had depleted both PCP and 5-HT2 receptors by 24 h after administration, but it failed to block 5-HT agonist 5-methoxy-N,N-dimethyltryptamine-induced 5-HT1A receptor-dependent behaviors. These results reconfirmed our hypothesis that PCP and 5-HT2 receptors may have very similar binding sites.

[Activation-induced changes in visual functions]. / Aktivierungsinduzierte Veränderungen visueller Funktionen.

Visual functions were tested in 18 healthy male medical students on a control day and on the day of an oral examination. Stress induced impairment was observed in binocular tests measuring accommodation, convergence or their mutual relationship (near points of accommodation and convergence, Maddox-wing). Results of tests in which fusion operates as stabilizing factor (slightly dissociating test: Polatest) or of tests designed for far distance vision (synoptophore, Maddox-cross, Pola-cross) did not show significant impairment under examination stress. In slightly dissociating tests an activity-dependent improvement in stereoscopic vision became evident. Flicker fusion frequency values increased under stress. Colour vision analysis by means of the Nagel anomaloscope revealed that the absolute matching range remained unchanged, whereas the relative matching range broadened on the day of examination. The results indicate activity-dependence of binocular vision, with an improvement in central nervous functions on the one hand and an impairment of peripheral accommodative components on the other hand. Furthermore, it may be concluded that binocular coordination is achieved independently from accommodation dependent focusing of the image and is apparently processed separately and parallel to monocular image components.

[Color vision in cataract, aphakia and pseudophakia]. / Farbensehen bei Katarakt, Aphakie und Pseudophakie.

Color vision examinations were performed using a clinical test battery and two spectral laboratory methods. With aphakia and iris-clip lenses (ICL) there were slight acquired blue-yellow defects six months to three years after surgery, especially when the more sensitive laboratory methods were used. They were possibly caused by photochemical damage to the retina or by a barrier deprivation syndrome. Color vision with posterior chamber lenses (PCL) was superior to that with ICL, and in aphakic subjects it was quite normal. In the clinical tests no differences could be found between PCLs of clear PMMA material and those with UV absorbing properties. Slight acquired blue-yellow defects in the immediate postoperative phase after implantation of PCLs can be attributed to postoperative irritation and are reversible. Lasting and severe blue-yellow defects indicate inflammation or macular edema.

[Modification of visual perception by vision training]. / Die Beeinflussung der visuellen Wahrnehmung durch Seh-Training.

The course of the visual pathway as far as the sulcus temporalis superior is described and the change in the shape of the receptive fields is pointed out. The transformation of action potentials into conscious perception is interpreted as it was by Eccles. A connection is made between the problem of learning and the plasticity of the spine synapses, the capacity of which can be considerably increased. In conclusion, it is pointed out that in cases of macular disease it is possible to stimulate peripheral areas of the visual field by special training and thus to help the visual field by special training and thus to help the patient.

[Significance of aniseikonia following implantation of posterior chamber lenses]. / Zur Bedeutung der Aniseikonie nach Implantation von Hinterkammerlinsen.

Posterior chamber lenses with angled haptics were implanted in one eye of each of 53 patients with senile cataract. Dioptric aniseikonia was calculated between 1 month and 24 months after surgery (with Gruber's and Huber's computer program) on the basis of most recently obtained values (bulb axis length, depth of the anterior chamber, lens thickness, necessary refraction), and compared with subjective measurements taken with the phase difference haploscope. The agreement between the calculated and subjective aniseikonia was greatest when tested in a vertical meridian. However, it was not possible to predict any correlation between dioptric and subjective aniseikonia with confidence. On the basis of the test results it seems justified to aim for a minimal refractive error in the pseudophakic eye of about +/- 0.5 D in patients with hypermetropia or myopia up to 4 D, even if subjective aniseikonias of over 10% can be proved. The latter manifest great meridional differences and hardly interfere with binocular single vision.

Oestrogen modulates dopamine-controlled behaviours in the male ferret.

Oestradiol (100 micrograms/kg) was administered to male ferrets on three successive days. Two and three days after the last oestradiol injection the effects of apomorphine (0.5 mg/kg) on stereotyped, predatory and scent marking behaviour were intensified. Thus, three days of oestradiol administration produced a supersensitive dopaminergic system two days after the last oestradiol injection. However, no initial antidopaminergic effect of oestradiol could be demonstrated one day after the last oestradiol injection.

Annual rhythm and hormonal control of predatory behavior in female ferrets.

The predatory behavior of female ferrets shows seasonal fluctuations which appear to be affected by estradiol. Under natural lighting conditions in the laboratory the annual rhythm of the behavior was observed during anestrus, estrus, pregnancy, pseudopregnancy and lactating period. Females in heat failed to show predatory behavior whereas females in anestrus killed their prey. Exposure of anestrous ferrets to a prolonged illumination (LD 16:8) during winter induced an estrus which inhibited predatory behavior. When estrus was terminated with human chorionic gonadotropin (HCG), predatory behavior did not further regress as it did in control runs. Thus, during the period of estrus, when estrogen levels are presumably high, predatory behavior was inhibited. To prove a possible interdependency of estrogen and predatory behavior, estradiol-17 beta-valerat was chronically administered. This treatment induced the estrous cycle one day after the first injection. Inhibition of predatory behavior occurred following a delay of 28 days. Thus, fluctuations of estradiol levels are a factor which may affect fluctuations of predatory behavior in female ferrets.

[Disorders of binocular vision in amblyopic patients working at computer terminals]. / Störung des Binokularsehens Amblyoper bei der Bildschirmarbeit.

For the first time two cases are described with disturbances of binocular vision caused by subjective perception of positive scotomata in the amblyopic eye. The visual strain of working at a terminal leads to a slight increase in the squint angle; as a result, a paracentral scotoma may shift into the middle of the binocular visual field and impair the image quality of the fixing eye. Amblyopic subjects presenting with these symptoms are disqualified from working at VDUs. However, not every amblyopic is affected.

[Topographic-anatomic position of the posterior chamber lens]. / Zur topographisch-anatomischen Lage der Hinterkammerlinse.

The present paper reports on a macroscopic and scanning electron microscope examination of a human cadaver eye with implanted posterior chamber lens (Simcoe type). The actual position of the lens haptics after planned sulcus ciliaris fixation is illustrated.

[Binocular vision following posterior chamber lens implantation]. / Binokularsehen nach Hinterkammerlinsenimplantation.

Binocular vision was tested in 106 pseudophakic patients 1 week after unilateral implantation of a Simcoe posterior chamber lens with 10 degrees angled haptics. Binocular functions are resumed immediately after surgery. Visual acuity, or rather the difference in visual acuity between the right and left eyes is mainly responsible for the quality of binocular vision. Heterophoria, anisometropia, and aniseikonia are less important.

[Differential diagnosis and therapy of gigantopapillary conjunctivitis]. / Zur Differentialdiagnose und Therapie der gigantopapillären Konjunktivitis.

If wearers of contact lenses present with secretion and incompatibility of the contact lens, simple ectropionation of the upper eyelids often is sufficient to diagnose a giant papillary conjunctivitis as the cause. This form of papillary hypertrophy affecting wearers of both hard and soft contact lenses is morphologically similar to vernal conjunctivitis, which should be considered in cases of corneal ulceration resistant to therapy. The histological difference between the two forms of papillary hypertrophy is that contact lens-induced giant papillary conjunctivitis shows remarkably less eosinophilic infiltration of the papillary stroma. Both forms of papillary hypertrophy seem to be based on a complex immunologic reaction.

[Central corneal endothelial changes in contact lens wearers]. / Zentrale Hornhautendothelveränderungen bei Kontaktlinsenträgern.

Report on the appearance of opacities in the central area of the cornea after long-term wearing of HEMA lenses. These changes are at first small curved spots and can develop into marked reticulate opacities at a late stage. All of the patients were long-term contact lens wearers and all used cleaning solutions containing chlorhexidine. Since early symptoms such as 'red eye' or 'blurred vision' are absent in most of the cases the patients fail to consult their doctors in time. The damage appears to be irreversible and early diagnosis is therefore important.

[Diagnosis and therapy of optic neuritis]. / Zur Diagnose und Therapie der Optikusneuritis.

Time-consuming and complicated electrophysiological methods need only be applied in unclear cases of optic neuritis. In the majority of patients it is possible to demonstrate opticus conduction disturbance with exact clinical subjective and objective tests. Some neuroophthalmological investigations that are well-suited for routine use are described more closely. Our own investigations of 190 patients demonstrated - in accordance with the modern medical literature - that the nowadays usual therapeutic measures do not influence the course of an optic neuritis essentially.

[Blind spot syndrome in convergent strabismus of the horror-fusionis type]. / Blind Spot Syndrom beim Konvergenzschielen vom Horror-Fusionis-Typ.

With reference to a case of convergent squint with early onset it is shown that a blind spot syndrome may develop if - in spite of sensory adaptation to the angle of squint - the patient lacks sufficiently deep suppression and the suppression scotoma is very small.

[Convergent strabismus with eccentric fixation in a case of persistent pupillary membrane]. / Strabismus convergens mit exzentrischer Fixation bei Membrana pupillaris persistens.

Case report of a now 9-year-old boy with a pronounced persistent pupillary membrane in both eyes combined with amblyopia and eccentric fixation in the right eye and a convergent squint. After surgery removing the persistent pupillary membrane in both eyes at the age of 4 years, pleoptics and orthoptics were applied. Visual acuity and eccentric fixation did not improve. Strabismic surgery was carried out with good cosmetic result. Aetiologically, one can assume a deprivation by the persisting pupillary membrane.