Pathogenic missense variation in PABPC1L/EPAB causes female infertility due to oocyte maturation arrest at the germinal vesicle stage.

Women undergoing controlled ovarian hyperstimulation prior to in vitro fertilization (IVF) are treated using various protocols to induce multiple follicular growths. Complete failure of all oocytes to mature during IVF cycles is rare; however, it is a known cause of primary female infertility. Recently, pathogenic variations in a few genes have been identified in women with oocyte maturation defects; however, the underlying genetic causes remain largely unknown.This study included a Turkish family comprising three sisters with recurring oocyte maturation arrest at the germinal vesicle stage after multiple ovarian stimulations. Exome sequencing revealed a homozygous missense variant (c.1037C>T, p.Ala346Val) in the EPAB gene (also known as PABPC1L) in all three affected sisters, which was either absent or heterozygous in the unaffected family members. Functional experiments confirming the pathogenicity of the variant were performed by transfecting HEK293T cells and demonstrated the instability and increased rate of proteolysis of the mutated PABPC1L/EPAB protein. The identified variant, located in the well-conserved fourth RNA recognition motif (RRM4), in silico 3D modelling suggested changes in the physical properties of the pathogenic variant of PABPC1L/EPAB. Our findings validate PABPC1L/EPAB as an essential genetic contributor to the oocyte maturation process in humans and have direct implications for the genetic counselling of patients and their family members.

RETROSPECTIVE STUDY OF MORBIDITY AND MORTALITY IN A CAPTIVE POPULATION OF CRYPTOSPORIDIUM-POSITIVE LOUISIANA PINE SNAKES (PITUOPHIS RUTHVENI).

The Louisiana pine snake (Pituophis ruthveni) is a diurnal colubrid species native to Louisiana and eastern Texas whose free-ranging populations have been declining over at least the past 30 yr. The creation and maintenance of sustainable captive breeding programs of P. ruthveni to restore native populations has also provided ample opportunity for research into this species and for P. ruthveni to serve as a research model for other colubrid snakes. However, no investigation into prevalent causes of morbidity and mortality in captive populations of this species has been described. A research population of P. ruthveni was maintained at Louisiana State University (LSU) for over 4 yr due to unsuitability for breeding after testing positive for Cryptosporidium serpentis. Since arrival at LSU, the snakes were under close veterinary surveillance. Complete postmortem examinations were performed on 12 snakes that died or were euthanized. The aim of this study was to further understanding of common factors influencing morbidity and mortality in captive P. ruthveni infected with C. serpentis, by retrospectively reviewing postmortem exam findings from the 12 deceased members of the population at LSU. A predominant finding across individuals included bacterial infections, which were responsible for major illness or death in 37.5% of the animals. Fifty percent of snakes tested positive for Cryptosporidium sp. based on PCR performed from postmortem samples; it was directly implicated as cause of death or morbidity in 83.3% of positive cases. Although infectious disease represented the most common pathologic postmortem finding, several noninfectious disease processes were identified, including gout, goiter, and neoplasia. These findings mirror those of other retrospective investigations of reptile collections at various institutions and highlight the need for appropriate emphasis on the identification, treatment, and prevention of infectious disease as part of routine veterinary care.

Sexual dimorphism in Louisiana pine snakes (Pituophis ruthveni).

The Louisiana pine snake, Pituophis ruthveni, is a cryptic, federally threatened snake species with several fragmented populations in Louisiana and Texas, USA. There are currently four captive breeding populations in zoos in the USA; however, little scientific data exists on their life history and anatomy. Accurate sex determination and identification of normal reproductive anatomy are an essential part of a veterinary exam and conservation programs. The authors had encountered various cases of sex misidentification in this species that were attributed to lack of lubrication of the sexing probes and enlarged musk glands. Anecdotal observation led to a hypothesis of sexual dimorphism based on body and tail shape. To test this hypothesis, we measured body length, tail length and width, and body to tail taper angle in 15 P. ruthveni (9 males and 6 females). We also obtained tail radiographs of all animals to document the presence of mineralized hemipenes. Significant dimorphism was identified in relative tail length, width, and taper angle; females consistently exhibited a more acute taper angle. Contrary to previous studies in other Pituophis species, a male-biased sexual size dimorphism was not identified. Mineralized hemipenes were confirmed in all males (a newly described trait in this species), and we found that the lateral view was consistently more reliable for identification of hemipenes compared to the ventrodorsal view. This information contributes to the scientific community's understanding of this species and is of use to biologists and veterinarians working toward conservation of this threatened species.

Nasopharyngeal versus nasal swabs for detection of SARS-CoV-2: a systematic review.

Nasopharyngeal swabbing (NPS) coupled with RT-PCR is the current gold standard for detecting SARS-CoV-2 infections. However, numerous studies have recently demonstrated the advantages of alternative nasal specimen collection approaches over NPS specifically for COVID-19 diagnosis. The present review was conducted according to PRISMA guidelines and summarises the current literature to give a clear overview of nasal specimen collection methods for SARS-CoV-2 detection. Publications investigating NPS and at least one other form of nasal specimen collection in combination with RT-PCR for viral detection in the context of COVID-19 were assessed. We identified 425 articles and ultimately included 18 studies in this systematic review. The suitable publications evaluated different forms of nasal specimen collection, with anterior nasal swabbing (ANS) and midturbinate swabbing (MTS) being the most frequently examined techniques. The analysed studies report sensitivity and specificity results (67.5-96.2% and 97.9-100.0%, respectively) similar to those achieved via NPS, especially in the early stages of disease or when paired with an oropharyngeal swab. Results from these studies suggest that ANS and MTS are suitable alternatives to NPS for COVID-19 testing. Due to their ease of collection, ANS and MTS collection techniques may facilitate broader testing strategies and allow for economization of medical staff.

Caffeine prevents prostaglandin E1-induced disturbances in respiratory control in neonatal rats: implications for infants with critical congenital heart disease.

Continuous infusion of prostaglandin E1 (PGE1) is used to maintain ductus arteriosus patency in infants with critical congenital heart disease, but it can also cause central apnea suggesting an effect on respiratory neural control. In this study, we investigated whether 1) PGE1 inhibits the various phases of the acute hypoxic ventilatory response (HVR; an index of respiratory control dysfunction) and increases apnea incidence in neonatal rats; and 2) whether these changes would be reversible with caffeine pretreatment. Whole body plethysmography was used to assess the HVR and apnea incidence in neonatal rats 2 h following a single bolus intraperitoneal injection of PGE1 with and without prior caffeine treatment. Untreated rats exhibited a biphasic HVR characterized by an initial increase in minute ventilation followed by a ventilatory decline of the late phase (~5th minute) of the HVR. PGE1 had a dose-dependent effect on the HVR. Contrary to our hypothesis, the lowest dose (1 µg/kg) of PGE1 prevented the ventilatory decline of the late phase of the HVR. However, PGE1 tended to increase postsigh apnea incidence and the coefficient of variability (CV) of breathing frequency, suggesting increased respiratory instability. PGE1 also decreased brainstem microglia mRNA and increased neuronal nitric oxide synthase (nNOS) and platelet-derived growth factor-ß (PDGF-ß) gene expression. Caffeine pretreatment prevented these effects of PGE1, and the adenosine A2A receptor inhibitor MSX-3 had similar preventative effects. Prostaglandin appears to have deleterious effects on brainstem respiratory control regions, possibly involving a microglial-dependent mechanism. The compensatory effects of caffeine or MSX-3 treatment raises the question of whether prostaglandin may also operate on an adenosine-dependent pathway.

Maternal risk factors and adverse birth outcomes associated with HELLP syndrome: a population-based study.

OBJECTIVES: We assessed the incidence, risk factors and adverse birth outcomes associated with elevated liver enzymes and low platelets (HELLP) syndrome. DESIGN: A retrospective population-based cohort study. SETTING: Canada (excluding Quebec), 2012/2013-2015/2016. POPULATION: Mothers with a singleton hospital live birth or stillbirth at ≥24 weeks' gestation (n = 1 078 323). METHODS: HELLP syndrome was identified using ICD-10-CA diagnostic code from delivery hospitalisation data. We used logistic regression to identify independent risk factors for HELLP syndrome by obtaining adjusted odds ratios (AOR) and 95% confidence intervals (CI), and to assess the associations with adverse outcomes. MAIN OUTCOME MEASURES: Adverse maternal (e.g. eclampsia) and fetal/neonatal outcomes (e.g. intraventricular haemorrhage, perinatal death). RESULTS: The incidence of HELLP syndrome was 2.5 per 1000 singleton deliveries (n = 2663). Risk factors included: age ≥35 years, rural residence, nulliparity, parity ≥4, pre-pregnancy and gestational hypertension and diabetes, assisted reproduction, chronic cardiac conditions, systemic lupus erythematosus, obesity, chronic hepatic conditions, placental disorders (e.g. fetomaternal transfusion) and congenital anomalies. PROM and age <25 years were inversely associated with HELLP syndrome (P-values <0.05). Women with the syndrome had a 10-fold higher maternal mortality (95% CI 1.6-84.3) and elevated severe maternal morbidity (9.6 versus 121.7 per 1000; AOR 12.5, 95% CI 11.1-14.1); and higher perinatal mortality (4.3 versus 21.0 per 1000; AOR 4.5, 95% CI 3.5-5.9) and perinatal mortality/severe neonatal morbidity (21.2 versus 202.4 per 1000; AOR 10.7, 95% CI 9.7-11.8). CONCLUSION: HELLP syndrome is associated with specific pre-pregnancy and pregnancy risk factors, higher rates of maternal death, and substantially higher severe maternal morbidity, perinatal mortality and severe neonatal morbidity. TWEETABLE ABSTRACT: HELLP syndrome is associated with higher maternal death rate, and substantially higher severe maternal and neonatal morbidity, and perinatal mortality.

Role of the Streptomyces spore wall synthesizing complex SSSC in differentiation of Streptomyces coelicolor A3(2).

A crucial stage of the Streptomyces life cycle is the sporulation septation, a process were dozens of cross walls are synchronously formed in the aerial hyphae in a highly coordinated manner. This process includes the remodeling of the spore envelopes to make Streptomyces spores resistant to detrimental environmental conditions. Sporulation septation and the synthesis of the thickened spore envelope in S. coelicolor A3(2) involves the Streptomyces spore wall synthesizing complex SSSC. The SSSC is a multi-protein complex including proteins directing peptidoglycan synthesis (MreBCD, PBP2, Sfr, RodZ) and cell wall glycopolymer synthesis (PdtA). It also includes two eukaryotic like serin/threonine protein kinases (eSTPK), PkaI and PkaH, which were shown to phosphorylate MreC. Since unbalancing phosphorylation activity by either deleting eSTPK genes or by expressing a second copy of an eSTPK gene affected proper sporulation, a model was developed, in which the activity of the SSSC is controlled by protein phosphorylation.

[Handball injuries and their prevention]. / Verletzungen und deren Prävention beim Handball.

BACKGROUND: Handball is one of the most popular team sports in Germany, as well as one of the most dangerous ones. Injury rates in Germany are higher amongst handball professionals than in soccer, with the knee being the most commonly injured joint. To prevent injuries, a functional inert stability is necessary, but definitions and objective measures are lacking. OBJECTIVES: Establishing valid reference data of functional knee stability in amateur handball players with use of an established test battery giving objective measures METHODS: 261 athletes (f:130; m:131), mean age 25.1 ± 5.8 y were screened during the preseason. The test battery consisted of double and single-leg counter movement jumps, balance tests, agility, parkour, quick feet test and plyometric jumps. RESULTS: Significant differences between males and females were noted in regard to balance scores (favour for females p ≤ 0.001), as well as jump height, agility and speed tests (favour for males [p ≤ 0.002-0.001]). CONCLUSION: The noted differences once again bring focus to the interindividual presence of risk factors, because female and male handball athletes have gender-specific ground levels. These attributes have to be considered in further screening and prevention programs, as well as in the context of the return-to-sports decision after injury. The given data may serve as objective reference measures.

Detection of blood Gb3 deposits as a new tool for diagnosis and therapy monitoring in patients with classic Fabry disease.

BACKGROUND: The X-linked Fabry disease (FD) is a multiorgan disorder due to alpha-galactosidase A (α-GAL) deficiency with consequent lysosomal accumulation of globotriaosylceramide (Gb3). We established the immunocytochemical detection of Gb3 in blood cells of FD patients as a new method for FD diagnostics, follow-up and treatment control. METHODS: We enrolled 67 FD patients (37 men, 30 women) and 52 healthy controls (26 men, 26 women). PBMC were isolated from whole venous blood and 3x105 cells were immunoreacted with antibodies against CD77 as a marker for Gb3. Using fluorescence microscopy, the mean percentage of Gb3 positive PBMC was determined by an investigator blinded to subject allocation. As a second method, we qualitatively assessed Gb3 positive cells in blood smears. RESULTS: Gb3 deposits were unequivocally visible in PBMC and in blood smears. Men (P < 0.001) and women (P < 0.01) with classical FD had more Gb3-positive PBMC than healthy controls, whose samples only occasionally showed positive cells. The number of Gb3 positive PBMC was negatively correlated with α-GAL activity and positively correlated with plasma lyso-Gb3 levels. Only the PBMC Gb3 load but not plasma lyso-Gb3 reflected short- and long-term effects of enzyme replacement therapy (P < 0.01). CONCLUSIONS: Gb3 can be visualized in PBMC and blood smears and can be used as a novel marker for diagnostics, follow-up and treatment control in FD.

Respiratory dysfunction following neonatal sustained hypoxia exposure during a critical window of brain stem extracellular matrix formation.

The extracellular matrix (ECM) modulates brain maturation and plays a major role in regulating neuronal plasticity during critical periods of development. We examined 1) whether there is a critical postnatal period of ECM expression in brain stem cardiorespiratory control regions and 2) whether the attenuated hypoxic ventilatory response (HVR) following neonatal sustained (5 days) hypoxia [SH (11% O2, 24 h/day)] exposure is associated with altered ECM formation. The nucleus tractus solitarius (nTS), dorsal motor nucleus of the vagus, hypoglossal motor nucleus, cuneate nucleus, and area postrema were immunofluorescently processed for aggrecan and Wisteria floribunda agglutinin (WFA), a key proteoglycan of the ECM and the perineuronal net. From postnatal day ( P) 5 ( P5), aggrecan and WFA expression increased postnatally in all regions. We observed an abrupt increase in aggrecan expression in the nTS, a region that integrates and receives afferent inputs from the carotid body, between P10 and P15 followed by a distinct and transient plateau between P15 and P20. WFA expression in the nTS exhibited an analogous transient plateau, but it occurred earlier (between P10 and P15). SH between P11 and P15 attenuated the HVR (assessed at P16) and increased aggrecan (but not WFA) expression in the nTS, dorsal motor nucleus of the vagus, and area postrema. An intracisternal microinjection of chondroitinase ABC, an enzyme that digests chondroitin sulfate proteoglycans, rescued the HVR and the increased aggrecan expression. These data indicate that important stages of ECM formation take place in key brain stem respiratory neural control regions and appear to be associated with a heightened vulnerability to hypoxia.

[Big data and deep learning in preventive and rehabilitation medicine]. / Big Data und maschinelles Lernen bei Prävention und Rehabilitation.

The digitalization in medicine has led to almost universal availability of information to different healthcare professionals and accelerated clinical pathways. Fast-track concepts and short hospital stays require intelligent and practicable systems in preventive and rehabilitation medicine. This includes optimization of movement analysis by innovative tools such as detectors sensing skin movements, portable feedback systems for monitoring, robot-assisted devices, and prevention programs based on reliable data. Finally, clinical structures are needed to exploit the maximal potential of artificial intelligence (AI) and deep learning. One example is the establishment of inter- and transdisciplinary professional teams such as a RehaBoard. In contrast to other cost-intensive disciplines such as oncology, the introduction of AI into rehabilitation orthopedics and trauma surgery with the support of cross-sectoral cooperation has great potential for performing well in patient benefit-orientated competition (value-based competition).

[Cavernomas of the central nervous system : Observational study of 111 patients]. / Kavernome des Zentralnervensystems : Verlaufsbeobachtung bei 111 Patienten.

PURPOSE: The prevalence of cavernomas (cavernous hemangioma) is 0.1-0.7%. Cavernomas are often found as an incidental finding within the framework of magnetic resonance imaging (MRI) examinations in mainly young and healthy patients. In the literature, the reported risk of hemorrhage varies greatly and is sometimes higher than that of aneurysms, which is surprising given that cavernomas are part of the low blood pressure system. After the diagnosis the medical practitioner and the patient have to decide on the further therapy, either surgical removal or the strategy of watchful waiting (conservative treatment). The aim of our study was to determine the frequency of bleeding of cavernomas and the consequences and to determine the satisfaction of patients with treatment. All these aspects should make the therapeutic decision easier for medical practitioners. MATERIAL AND METHODS: The study included all patients who were treated in the military hospital in Ulm during the period 2002-2012 and with the diagnosis of one or more cavernomas of the central nervous system (CNS) detected by MRI. This resulted in a total number of 111 patients. We recorded the epidemiological data and analyzed all cavernomas with respect to the location, size, treatment, side effects, etc. Furthermore, all included patients were sent a comprehensive questionnaire about symptoms, course of the disease and the quality of life. The response rate was 38%. All the collected data were analyzed with respect to the various aspects. RESULTS: Depending on the definition of a bleeding event of a cavernoma and selection of the observational period, the probability of a hemorrhage risk ranged from 1.3% to 5.9% per patient year. This relatively high proportion is, however, put into perspective by the mostly mild consequences of a bleeding event. Many cavernomas, which were detected as an incidental finding showed signs of previous bleeding but the patients remained free of symptoms. Additionally, there was no patient in this collective who suffered serious consequences due to a bleeding event. Of the patients with temporal cavernomas 45% had symptomatic epilepsy. The results of the patient survey were heterogeneous. Some patients stated that in retrospect they would not choose surgical treatment again. CONCLUSION: As a result of our findings we think it is important to critically look at the indications for surgical removal of cavernomas and special attention must be paid to informed consent of the patient. The frequent appearance of temporal cavernomas and their propensity to epileptic seizures is an essential aspect, which certainly influences the therapeutic decision. Although cavernomas are a venous malformation in the low blood pressure system, the determined frequency of hemorrhage was 5.9%, which was higher than expected but which is confirmed by other studies. Reports on severe sequelae of cavernoma bleeding are also rare in the literature, which relativizes the resulting danger of the relatively high probability of hemorrhage.

[Interventional radiology in the head and neck region]. / Interventionelle Radiologie im Kopf-Hals-Bereich.

In interventional neuroradiology, endovascular embolization represents an important and helpful tool in the treatment of multiple head and neck diseases. These interventional procedures may be performed with curative intent, to reduce the surgical risk within a multimodal treatment concept, or to improve or at least maintain a good quality of life within a palliative therapy concept. In addition to a good understanding of disease pathology, knowledge of vascular anatomy, including collateral vessels and dangerous extracranial-intracranial anastomoses, is essential for successful treatment, as is implementation of an established technique using appropriate material. Indications for endovascular embolization are i. otherwise unmanageable bleeding (caused by e. g., trauma, vascular malformation, or tumor), ii. reduction of perioperative bleeding by preoperative embolization in case of a hypervascularized tumor, iii. selective induction of tumor necrosis by palliative embolization to enhance local tumor control. Major complications such as stroke, loss of vision, and cranial nerve palsy are mostly due to a lack of preinterventional evaluation. Regarding neurological deficits, interventions within the supply region of the external carotid artery have a complication rate below 1%.

Microglia modulate brainstem serotonergic expression following neonatal sustained hypoxia exposure: implications for sudden infant death syndrome.

KEY POINTS: Neonatal sustained hypoxia exposure modifies brainstem microglia and serotonin expression. The altered brainstem neurochemistry is associated with impaired ventilatory responses to acute hypoxia and mortality. The deleterious effects of sustained hypoxia exposure can be prevented by an inhibitor of activated microglia. These observations demonstrate a potential cause of the brainstem serotonin abnormalities thought to be involved in sudden infant death syndrome. ABSTRACT: We showed previously that the end of the second postnatal week (days P11-15) represents a period of development during which the respiratory neural control system exhibits a heightened vulnerability to sustained hypoxia (SH, 11% O2 , 5 days) exposure. In the current study, we investigated whether the vulnerability to SH during the same developmental time period is associated with changes in brainstem serotonin (5-HT) expression and whether it can be prevented by the microglia inhibitor minocycline. Using whole-body plethysmography, SH attenuated the acute (5 min) hypoxic ventilatory response (HVR) and caused a high incidence of mortality compared to normoxia rats. SH also increased microglia cell numbers and decreased 5-HT immunoreactivity in the nucleus of the solitary tract (nTS) and dorsal motor nucleus of the vagus (DMNV). The attenuated HVR, mortality, and changes in nTS and DMNV immunoreactivity was prevented by minocycline (25 mg kg(-1) /2 days during SH). These data demonstrate that the 5-HT abnormalities in distinct respiratory neural control regions can be initiated by prolonged hypoxia exposure and may be modulated by microglia activity. These observations share several commonalities with the risk factors thought to underlie the aetiology of sudden infant death syndrome, including: (1) a vulnerable neonate; (2) a critical period of development; (3) evidence of hypoxia; (4) brainstem gliosis (particularly the nTS and DMNV); and (5) 5-HT abnormalities.

Aii20J, a wide-spectrum thermostable N-acylhomoserine lactonase from the marine bacterium Tenacibaculum sp. 20J, can quench AHL-mediated acid resistance in Escherichia coli.

Acyl homoserine lactones (AHLs) are produced by many Gram-negative bacteria to coordinate gene expression in cellular density dependent mechanisms known as quorum sensing (QS). Since the disruption of the communication systems significantly reduces virulence, the inhibition of quorumsensing processes or quorum quenching (QQ) represents an interesting anti-pathogenic strategy to control bacterial infections. Escherichia coli does not produce AHLs but possesses an orphan AHL receptor, SdiA, which is thought to be able to sense the QS signals produced by other bacteria and controls important traits as the expression of glutamate-dependent acid resistance mechanism, therefore constituting a putative target for QQ. A novel AHL-lactonase, named Aii20J, has been identified, cloned and over expressed from the marine bacterium Tenacibaculum sp. strain 20 J presenting a wide-spectrum QQ activity. The enzyme, belonging to the metallo-ß-lactamase family, shares less than 31 % identity with the lactonase AiiA from Bacillus spp. Aii20J presents a much higher specific activity than the Bacillus enzyme, maintains its activity after incubation at 100 ºC for 10 minutes, is resistant to protease K and α-chymotrypsin, and is unaffected by wide ranges of pH. The addition of Aii20J (20 µg/mL) to cultures of E. coli K-12 to which OC6-HSL was added resulted in a significant reduction in cell viability in comparison with the acidresistant cultures derived from the presence of the signal. Results confirm the interaction between AHLs and SdiA in E. coli for the expression of virulence-related genes and reveal the potential use of Aii20J as anti-virulence strategy against important bacterial pathogens and in other biotechnological applications.

Effective local anaesthetic volumes for sciatic nerve blockade: a clinical evaluation of the ED99.

Previous results in volunteers have indicated the effective dose in 99% of subjects (ED99 ) of local anaesthetic volume to be 0.10 ml.mm(-2) of cross-sectional nerve area for sciatic nerve blockade. The objective of this prospective, randomised, double-blind study was to investigate the ED99 of local anaesthetic for ultrasound-guided sciatic nerve blockade in patients undergoing foot surgery, according to Dixon's up-and-down method and probit analysis. A starting volume of 0.20 ml local anaesthetic per mm(2) cross-sectional nerve area was used. If surgical anaesthesia was judged to be adequate, the volume of local anaesthetic for the next case was reduced by 0.02 ml.mm(-2), until the first block failed. Thereafter, the volume of local anaesthetic was increased by 0.02 ml.mm(-2). The ED99 volume of local anaesthetic for ultrasound-guided sciatic nerve blockade was calculated to be 0.15 ml.mm(-2) cross-sectional nerve area, which is higher than the previously evaluated ED99 volume in volunteers.

Predictive factors for intraocular pressure reduction after phacoemulsification in Swiss patients.

BACKGROUND: Phacoemulsification is known to induce postoperative intraocular pressure (IOP) reduction, the degree of which varies according to glaucoma subtype and race. The authors set out to investigate the effect of cataract surgery on IOP, in a Swiss Caucasian population, and identify ocular predictive factors. PATIENTS AND METHODS: 234 consecutive cases of 188 patients undergoing phacoemulsification between January 2011 and December 2012 were retrospectively reviewed and data collected. Exclusion criteria included acute angle closure, malignant glaucoma and pre-existing or subsequent glaucoma surgery. Pre- and post-operative visual acuity, IOP, gonioscopic findings, glaucoma medications, and laser treatments were recorded for eligible eyes. All eyes received the same postoperative regimen. Using multivariate analysis the predictive power of preoperative IOP, iridocorneal angle width, axial length on IOP reduction following phacoemulsification at months 3, 6 and 12 postoperatively were assessed. Eyes with narrow angles were compared against those with open angles. RESULTS: 172 eyes of 121 patients met the inclusion criteria; mean age was 70.3 years (SD±10.7 years), with 77 males. Preoperatively median IOP was 16 mmHg (range 9-32 mmHg), mean number of glaucoma medications was 1.2 (SD±1.1), median visual acuity was 0.28 LogMAR (range 0-2.3LogMar). At 3 months post-operatively mean IOP decreased to 14 mmHg (p<0.01) and remained statistically significantly reduced until 12 months, mean number of glaucoma medications was reduced to 1.0 and mean Snellen visual acuity increased to 0.8. Multivariate analysis revealed that pre-operative IOP and iridocorneal angle width (at 3 months) were significant predictive indicators of IOP reduction. At 12 months, IOP reduction was similar between open and narrow angle groups and total IOP reduction was no longer statistically significant. No intraoperative complications were recorded. CONCLUSIONS: Intraocular pressure reduction following phacoemulsification was greatest during the very early post-operative period, particularly in narrow angle patients. By one year, angle size was no longer predictive of IOP lowering, however pre-operative IOP and number of anti-glaucoma medications remained correlated with total IOP reduction.

[Morphological Characteristics in SD-OCT and Fundus Autofluorescence in Different Ischaemic Retinopathies - Characterisation of a New, Temporary Hyperreflective Band]. / Morphologische Charakteristika im hochauflösenden OCT und in der Fundusautofluoreszenz bei verschiedenen ischämischen Retinopathien - Beschreibung einer zusätzlichen, temporären hyperreflektiven Bande.

BACKGROUND: The aim of this study was to investigate alterations in the neurosensory retinal morphology secondary to acute retinal ischaemic conditions. The observations were documented by spectral domain optical coherence tomography (SD-OCT, Heidelberg Engineering) and fundus autofluorescence (FAF) imaging. In addition, the occurrence of an additional hyperrefelctive band in the outer corneal layers is described. This observation was made during the evaluation of OCT images of patients with an acute loss of vision due to retinal ischaemia. PATIENTS/METHOD: SD-OCT images and FAF were used to observe the retinal structure of 26 subjects (36 to 96 years) with acute monocular visual impairment due to central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO), anterior ischaemic optic neuropathy (AION) or impending central retinal vein occlusion were included. The main focus of attention was set on the transition of the outer nuclear layer (ONL) to outer plexiform layer (OPL). Furthermore measurements of the retinal thickness at the fovea, parafoveal and within the retinal layers were acquired and compared to corresponding points of the non-affected eyes. SD-OCT images were acquired with a combined SD-OCT and scanning laser ophthalmoscope (cSLO) imaging system using a linear cross hair scan and a 6 line radial scan of 6 mm length (ART mode on; average of 20 frames). RESULTS: SD-OCT revealed an additional highly reflective band located within the OPL. Morphological characteristics of this hyperdense band were a decreasing intensity with distance from the fovea, partially segmental occurrence and manifestation limited in time. FAF showed areas of increased and decreased signal intensity within the vessel arcade at the posterior pole. The regions of decreased FAF corresponded to perivenous regions and resemble the "frosted branches" sign seen in fluorescein angiography in patients with ocular ischaemia. CONCLUSIONS: The additional hyperreflective band observed in SD-OCT could represent a marker for retinal ischaemia in subjects without the presence of a complete vascular occlusion. The mid retinal localisation of the band within the OPL is situated at the locus of transition from retinal to choroidal oxygen supply where oxygen diffusion is weakest. Histopathologically the observed structure could represent activated microglial tissue induced by the hypoxia driven upregulation of inflammatory molecules aimed at ischaemia repair.

Anti-CD4 treatment inhibits autoimmunity in scurfy mice through the attenuation of co-stimulatory signals.

A major concept in autoimmunity is that disruption of Foxp3(+) regulatory T cells (Tregs) predisposes to breach of tolerance. This is exemplified by the Foxp3-linked disorder termed IPEX (immunodysregulation, polyendocrinopathy, enteropathy, X-linked) which affects newborn children. There has been considerable clinical interest in the role of non-depleting anti-CD4 antibodies as a means of upregulating the function of Foxp3(+) Tregs in order to control detrimental inflammatory responses such as transplant rejection. However, according to the paradigm of a Treg-dependent mechanism of action, the effectiveness of anti-CD4 antibodies as a therapy for human autoimmune diseases is unclear considering that Treg function might be intrinsically impaired. Specifically, anti-CD4 therapy is expected to fail in patients suffering from the IPEX syndrome due to the lack of functional Foxp3(+) Tregs. Taking advantage of natural Foxp3 mutant scurfy (sf) mice closely resembling the IPEX syndrome, and genetically engineered mice depleted of Foxp3(+) Tregs, we report here that anti-CD4 treatment induces tolerance independent of Foxp3(+) Tregs. This so far undefined mechanism is dependent on the recessive non-infectious tolerization of autoreactive T cells. Treg-independent tolerance alone is powerful enough to suppress both the onset and severity of autoimmunity and reduces clinically relevant autoantibody levels and liver fibrosis. Mechanistically, tolerance induction requires the concomitant activation of autoreactive T cells and is associated with the down-regulation of the co-stimulatory TNF-receptor superfamily members OX40 and CD30 sustaining CD4(+) T cell survival. In the light of ongoing clinical trials, our results highlight an unexpected potency of anti-CD4 antibodies for the treatment of autoimmune diseases. Particularly, CD4 blockade might represent a novel therapeutic option for the human IPEX syndrome.

Influence of spatial distribution and size of clones on the realized outcrossing rate of the marsh cinquefoil (Comarum palustre).

BACKGROUND AND AIMS: Clonal growth is a common feature in flowering plants. As clone size increases, the selfing rate in self-compatible species is likely to increase due to more frequent geitono-pollination events (i.e. pollination among flowers within the same genet). This study investigated the breeding system of the marsh cinquefoil (Comarum palustre) and assessed spatial distribution of clones, clone size and architecture, and their effects on realized outcrossing rates. In addition, pollen dispersal was investigated in two patchy populations. METHODS: The species' breeding system was investigated under controlled conditions through hand pollinations (self- vs. cross-pollination). Using microsatellite markers, an assessment was made of the realized outcrossing rates and the genetic diversity in four natural populations, the clonal structure in two populations within five 15 × 15 m sampling plots following 0.5 × 0.5 m grids, and the pollen dispersal through paternity assignment tests in those two populations. KEY RESULTS: Comarum palustre is a self-compatible species but only presents a low rate of spontaneous self-pollination. The occurrence of inbreeding depression was not detected at the seed set stage (δ(SS) = 0.04). Clones were spatially clumped (A(C) = 0.60-0.80), with intermediate to no intermingling of the ramets (D(C) = 0.40-1.00). Genet size ranged from one to 171 ramets. Patchy populations had low outcrossing rates (t(m) = 0.33-0.46). Large clones showed lower outcrossing rates than small clones. Pollen dispersal mainly occurred within patches as only 1-7 % of the pollination events occurred between patches of >25 m separation. Seedling recruitment events were detected. CONCLUSIONS: Genet size together with distances between patches, through increasing geitono-pollination events, appeared to be important factors influencing realized outcrossing rates. The study also revealed seed flow allowing seedling recruitment, which may contribute to increasing the number of new patches, and potentially further enhance gene flow within populations.