bluuebunny/crossref_metadata_2025 huggingface dataset:
Parallel allochronic divergence in a winter moth due to disruption of reproductive period by winter harshness
Authors: YAMAMOTO SATOSHI , SOTA TEIJI
Published: November 2011

The disruption of reproductive timing by climatic harshness may result in the temporal isolation of conspecific populations and, ultimately, in speciation. However, whether temporal isolation alone can act as the force initiating speciation and how often the same type of climatic disruption results in the divergence of allochronic populations in a lineage are largely unknown. The reproductive period of the winter geometrid moth Inurois punctigera is separated into early and late winter in habitats with severe winters, but not in habitats with mild winters, suggesting that the reproductive season is disrupted by the harshness of the mid‐winter period. Here, we show that sympatric pairs of early‐ and late‐winter populations that differ in origin exist in different regions, suggesting a parallel divergence of reproductive timing. In each region, significant genetic differentiation exists between these early‐ and late‐winter populations, suggesting that the temporal reproductive isolation has persisted. Moreover, we demonstrate that the temporal isolation, in comparison with geographic isolation, contributes greatly to the genetic differentiation among geographic and temporal populations by an analysis of molecular variance and by a comparison of genetic differentiations (FST) between geographic populations with and without difference in reproductive season. Our results suggest that adaptive divergence of allochronically reproducing populations has occurred independently in different regions, implying the generality of the role of temporal isolation in initiating speciation in a winter moth lineage.
The Holocene shallowing‐upward parasequence of north‐west Andros Island, Bahamas
Authors: MALOOF ADAM C. , GROTZINGER JOHN P.
Published: November 2011

Many pre‐Mesozoic records of Earth history are derived from shallow water carbonates deposited on continental shelves. While these carbonates contain geochemical proxy records of climate change, it is the stratal architecture of layered carbonate units that often is used to build age models based on the idea that periodic astronomical forcing of sea‐level controls the layering. Reliable age models are crucial to any interpretation of rates and durations of environmental change, but the physical processes that actually control this stratal architecture in shallow water carbonates are controversial. In particular, are upward‐shallowing stacks of carbonate beds bounded by flooding surfaces (‘parasequences’) truly a record of relative sea‐level change? The purpose of this study is to examine a tidal flat that is actively accumulating carbonate stratigraphy, and to determine the relative importance of tidal channel migration (poorly known, but investigated here) and Holocene sea‐level rise (well‐known) in controlling post‐glacial parasequence architecture. This work represents a field study of peritidal carbonate accumulation at Triple Goose Creek, north‐west Andros Island. By integrating surface facies maps with differential global positioning system topographic surveys, a quantitative relationship between facies and elevation is derived. Sedimentary facies are sensitive to elevation changes as small as 5 cm, and are responding to both internal (distance to nearest tidal channel) and external (sea‐level rise) controls. The surface maps also are integrated with 187 sediment cores that each span the entire Holocene succession. While flooding of the Triple Goose Creek area should have occurred by ca 4500 years ago, preservation of Holocene sediment did not begin until 1200 years ago. The tidal channels are shown to be stationary, or to migrate sluggishly at up to 6 cm per year. Therefore, while the location of tidal channels is responsible for the modern mosaic of surface facies, these facies and the channels that control them have not migrated substantially during the ca 1200 years of sediment accumulation at Triple Goose Creek. Once the region was channellized, vertical and lateral shifts in facies, such as the landward retreating shoreline, expanding mangrove ponds and seaward advancing inland algal marsh, are driven by changes in relative sea‐level and sediment supply, not migrating channels. While stratigraphic columns look different depending on the distance to the nearest tidal channel, the overall parasequence architecture everywhere at Triple Goose Creek records an upward‐shallowing trend controlled by the infilling of accommodation space generated by post‐glacial sea‐level rise.
Correlation and agreement of self‐assessed and objective skin disease severity in a cross‐sectional study of patients with acne, psoriasis, and atopic eczema
Authors: Magin Parker J. , Pond C. Dimity , Smith Wayne T. , Watson Alan B. , Goode Susan M.
Published: November 2011

Background  Previous studies have shown variable correlation of patients’ self‐assessed skin severity measures and clinician‐assessed objective measures of severity. But, generally, correlation has not been as good as might be expected for conditions in which the objective physical extent of skin disease is apparent to the sufferer to an extent that is not applicable in many other diseases.

Methods  This paper reports agreement and correlation of self‐assessed and objective severity measures in a study of 108 subjects with acne, psoriasis, or atopic eczema. The study was a cross‐sectional study examining psychological associations of these skin diseases. Objective severity was assessed with the Leeds technique (acne), the Psoriasis Area and Severity Index, and Six Area Six Sign Atopic Dermatitis instruments. Agreement is a more appropriate measure than correlation in this situation and was measured with weighted kappa, while correlation was measured with Spearman’s rank correlation.

Results  There was a modest correlation of ρ = 0.46 and similarly very modest agreement of 0.35 (weighted kappa) of self‐assessed and clinician‐assessed disease severity. Furthermore, self‐assessed (but not clinician‐assessed) severity was statistically associated with psychological morbidity in this study; i.e. – depression, anxiety, and overall psychological morbidity.

Conclusions  Clinicians should consider psychological sequelae of skin disease, not only in those with objectively more severe disease but in patients across the severity spectrum. Both observational and interventional studies of skin disease should include both clinician‐assessed and self‐assessed measures of severity among assessed variables.
Radiotherapy‐induced pemphigus vulgaris with autoantibodies targeting a 110 kDa epidermal antigen
Authors: Badri Talel , Hammami Houda , Lachkham Ali , Benmously‐Mlika Rym , Mokhtar Inçaf , Fenniche Samy
Published: November 2011

Background  Pemphigus is an autoimmune intraepidermal blistering disease mediated by autoantibodies targeting desmosomes. It can be induced by many triggers, such as ionizing radiation.

Methods  We report a case of radiotherapy‐induced pemphigus (RIP) with a review of the published cases in the English and French literature.

Results  A 61‐year old man was diagnosed to have epidermoid carcinoma of the piriform sinus and then received a 70 Gy radiation therapy. One month after the treatment completion, multiple blisters and erosions occurred initially on the site of irradiation, then in other skin areas. Histological examination showed an intraepidermal blister with acantholysis and necrosis of individual keratinocytes. Direct immunofluorescence and indirect immunofluorescence were typical of pemphigus. Immunoblot revealed antibodies reacting with a 110 kDa antigen. This feature was consistent with the diagnosis of RIP. Less than 20 cases of RIP have been reported previously. Mean age at diagnosis was 64.2 years, and there is a slight female preponderance. RIP occurred, in most cases, initially within the area of irradiation.

Conclusion  Our patient showed some distinctive findings never reported previously in RIP: a histological focal keratinocyte necrosis, and the presence of autoantibodies reacting with a 110 kDa keratinocytic protein in immunoblot analysis. Because of a different prognosis, it is important to differentiate RIP and paraneoplastic pemphigus (PNP), although cases of ionizing radiation‐induced PNP had also been described. As in our patient, RIP seems to respond well to systemic corticosteroids and immunosuppressive therapy, which induce remission within a few months.
Linear sclerodermic lupus erythematosus, a distinct variant of linear morphea and chronic cutaneous lupus erythematous
Authors: Khelifa Elhem , Masouye Isabelle , Pham Hoang Chinh , Parmentier Laurent , Borradori Luca
Published: November 2011

Background  Overlap syndromes represent disorders that combine diagnostic criteria of two or more different connective tissue diseases.

Methods  We herein describe the case of a 34‐year‐old patient.

Results  Our patient developed a lesion on the scalp and forehead following Blaschko’s line typical for linear morphea “en coup de sabre”, while histopathological features were consistent with both chronic cutaneous lupus erythematosus and linear morphea, a cutaneous overlap syndrome previously described as linear sclerodermiform lupus erythematosus. The patient was given oral antimalarials in association with topical steroids and calcineurin inhibitors with good response.

Conclusions  Knowledge of this peculiar cutaneous overlap syndrome is warranted, since its management and prognosis is probably different from classical linear morphea.
Interesting effect of Malassezia spp. infection on dermatoses of other origins
Authors: Pakran Jaheersha , Riyaz Najeeba
Published: November 2011

Background  Tinea versicolor (TV) is a superficial fungal infection affecting as many as 40% of the population in the tropics. We noticed an unusual affect of TV on dermatoses of other origins.

Methods  In this prospective clinical study, we examined patients attending our dermatology outpatient department over a period of one year for coexistence of TV with any unrelated dermatoses. We confirmed the diagnosis of TV by microscopy of skin scrapings. Skin biopsy was performed when necessary to confirm the diagnosis of associated dermatoses.

Results  We describe four cases in which unrelated dermatoses (viral exanthem, acute generalized exanthematous pustulosis, polymorphous light eruption, and irritant contact dermatitis) specifically spared sites affected with TV.

Conclusions  Recent research has elucidated the immunomodulatory properties of Malassezia spp. in vitro. Our cases serve as possible in vivo models illustrating such properties. Further studies based on these reports could lead to the isolation of molecules from Malassezia, which may have potential use in anti‐inflammatory drug formulations.
Diagnosing leprosy: revisiting the role of the slit‐skin smear with critical analysis of the applicability of polymerase chain reaction in diagnosis
Authors: Banerjee Surajita , Biswas Nibir , Kanti Das Nilay , Sil Amrita , Ghosh Pramit , Hasanoor Raja Abu Hena , Dasgupta Sarbani , Kanti Datta Pijush , Bhattacharya Basudev
Published: November 2011

Background  Diagnosing leprosy is challenging, especially in early‐stage cases, and the need for a sensitive diagnostic tool is urgent. Polymerase chain reaction (PCR) holds promise as a simple and sensitive diagnostic tool, but its usefulness in the Indian context requires further evaluation. Slit‐skin smear (SSS) remains the conventional method of leprosy detection. Hence, this study was undertaken to evaluate and compare the diagnostic efficacy of PCR versus that of SSS.

Methods  Punch biopsy of skin and SSS were obtained from the active margins of lesions. Cases were clinically grouped according to whether they were multibacillary (MB) or paucibacillary (PB) and classified into tuberculoid (TT), borderline tuberculoid (BT), borderline lepromatous (BL), lepromatous (LL), histoid, and indeterminate groups after clinicopathological correlation. DNA was extracted from biopsy specimens, and multiplex PCR was carried out incorporating primers intended for the amplification of a specific 372‐bp fragment of a repetitive sequence of Mycobacterium leprae DNA.

Results  Among 164 patients, PCR was positive in 82.3%. The sensitivity of PCR was significantly greater (P < 0.0001) than that of SSS in both the MB (85.9% vs. 59.8%) and PB (75.4% vs. 1.8%) subgroups; the difference in sensitivity in the PB subgroup is remarkable. Positivity by PCR and SSS was found in 100% of LL and histoid leprosy, but PCR had significantly greater (P < 0.0001) positivity in BT leprosy and was of definite increased value in indeterminate and TT leprosy.

Conclusions  Polymerase chain reaction had higher sensitivity compared with SSS, especially in diagnostically challenging and PB cases. Thus, the use of this costly but sensitive tool should be restricted to this subgroup, because SSS is sufficiently sensitive in the diagnosis of LL and histoid leprosy.
Hematological abnormalities and the use of granulocyte‐colony‐stimulating factor in patients with Stevens–Johnson syndrome and toxic epidermal necrolysis
Authors: Ang Chia‐Chun , Tay Yong‐Kwang
Published: November 2011

Background  Derangements in blood cell counts have been described in patients with Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) but are not well characterized. We aim to describe the relationship between our patients’ hematological results and the evolution of disease and hypothesize on the possible roles of granulocyte‐colony‐stimulating factor (G‐CSF) in the management of these conditions.

Materials and methods  Clinical records of our patients with SJS and TEN from January 2005 to 2010 were analyzed.

Results  Anemia and lymphopenia were most commonly seen, while thrombocytopenia was uncommon. Leukopenia and neutropenia were seen in patients with more severe disease, and the trend of leukopenia and neutropenia followed the evolution of disease. Two patients received G‐CSF for febrile neutropenia and had a rapid recovery of their neutrophil counts as well as a shorter time to re‐epithelialization.

Conclusion  Our patients tended to have leukopenia and neutropenia that followed a predictable trend of decline and subsequent improvement depending on the stage of disease. This may be of pathogenic significance, and G‐CSF may be used in these cases to manage febrile neutropenia and aid re‐epithelialization. Further basic science research is required to prove our hypotheses.
A method for distinguishing the intended margins for a melanoma from the tissue cones after surgical excision
Authors: Kriegel David , Marmur Ellen , Shan Hui Yi , Mercer Stephen E. , Birge Miriam B. , Lee Arnold
Published: November 2011

Background  Surgical excision of severely dysplastic nevi and thin cutaneous melanomas (<1 mm in depth) remains the most effective treatment to date. However, sometimes a severely dysplastic nevus may be upstaged to a melanoma in situ, or a melanoma in situ may be upgraded to an invasive melanoma once the completely excised specimen is reviewed microscopically. This then requires a re‐excision around the entire scar at follow‐up as the dermatological surgeon can be perplexed as to where the precise locations of the pigmented lesion and the tissue cones are, thereby generating a longer scar.

Objective  We want to introduce a simple, cost‐effective and easy‐to‐implement approach that permits the dermatological surgeon to distinguish from a linear scar the site of the original pigmented lesion and the lengths of the tissue cones. Therefore, if a re‐excision is necessary, instead of surgical removal around the entire scar, only a focal directed excision of the pigmented lesion is necessary and this will result in a shorter scar; this will be useful for cosmetically sensitive areas on the face. A case is included to illustrate our objective.

Results and Discussion  Using our surgical method on a patient’s left cheek pigmented lesion originally diagnosed as melanoma in situ with a subsequent revised diagnosis of invasive melanoma generated a shorter scar and a favorable cosmetic outcome.
Systemic contact dermatitis
Authors: Veien Niels K.
Published: November 2011

Systemic contact dermatitis is an inflammatory skin disease that may occur in persons with contact allergy when they are exposed to the hapten orally, transcutaneously, per rectum, intravesically, intravenously, or by inhalation. The most common causes of systemic contact dermatitis are drugs used both topically and systemically. Other causes are ubiquitously occurring haptens, such as the metals nickel, cobalt, gold, and chromate, and aromatic substances such as spices. Avoidance of the offending hapten is the most obvious treatment. For some haptens, such as nickel, diet treatment may be effective. Chelation therapy with disulfiram is another therapeutic option in nickel‐allergic patients with systemic contact dermatitis. Hyposensitization therapy has been attempted with some success in systemic contact dermatitis caused by nickel andParthenium hysterophorus.
Heart rate limitation and cardiac unloading in sevoflurane post‐conditioning
Authors: LARSEN J. R. , SIVESGAARD K. , CHRISTENSEN S. D. , HØNGE J. L. , HASENKAM J. M.
Published: November 2011

Background

Sevoflurane post‐conditioning (SePost) has been found to alleviate ischemic myocardial reperfusion injury through the activation of prosurvival kinases. Lowered myocardial oxygen demand from reduced cardiac work may also contribute to cardioprotection, and is much less well‐studied. Our aim was to examine the simultaneous effects of SePost on cardiac work (here, rate–pressure product, RPP) and myocardial infarct size in a porcine model.

Methods

Anesthetized 25 kg pigs were randomly allocated to two groups and underwent 45 min regional coronary artery balloon occlusion and subsequent 2 h reperfusion. SePost (n = 10) was given as sevoflurane 1.5–3% end‐tidal concentration during reperfusion while controls (n = 12) were untreated. Aortic blood pressure was measured directly, while mixed‐venous oxygen saturation and cardiac output were measured in the pulmonary artery. Cardiac work was determined as RPP. Post‐mortem, histologic myocardial infarct size (IS), and area at risk were determined in transverse heart slices after tetrazolium stain.

Results

Myocardial infarct size was reduced from (control) 55.0 (mean) ± 13.6% (standard deviation) to 32.5 ± 13.4% in group SePost (P = 0.0009). During reperfusion, SePost resulted in lower heart rate (P = 0.0003), cardiac output (P = 0.0123), mixed‐venous oxygen saturation (P = 0.0103), blood pressure, and RPP (P < 0.0001). RPP was highly correlated to IS (P = 0.0055).

Conclusion

SePost (1.5–3%) reduced infarct size after regional myocardial ischemia in vivo and reduced cardiac work was significantly correlated to myocardial salvage.
Short stay and less pain after ambulatory anterior cruciate ligament (ACL) repair: COX‐2 inhibitor versus glucocorticoid versus both combined
Authors: DAHL V. , SPRENG U. J. , WAAGE M. , RAEDER J.C.
Published: November 2011

Background

Many studies have demonstrated that either COX‐2 antagonists or glucocorticoids are efficient analgesics after orthopaedic surgery. We wanted to evaluate if the combination of these two drugs was better than one drug alone when added to paracetamol, local anaesthesia, and cryo‐cuff for outpatient anterior crucial ligament (ACL) surgery.

Methods

In a double‐blind design, 89 adult patients scheduled for day‐case ACL repair in general anaesthesia were randomly assigned into three groups: The COXIB group (n = 30) received either 40 mg parecoxib iv or 120 mg etoricoxib orally 1 h before surgery. The STEROID group (n = 30) received 8 mg dexamethasone iv, and the combination group (Group COMBI, n = 29) received both.

Results

At 24 h, Group COMBI had significantly lower visual analogue scale (0–10 cm) scores during rest (2.1 ± 1.3) (mean ± standard deviation) and movement (4.2 ± 2.5) when compared to both the COXIB group (P = 0.04) and the STEROID group (P = 0.035). The accumulated consumption of rescue opioids (5.2 ± 4,5 mg morphine) was also significantly lower at 24 h compared to the other groups (P = 0.02). Mean time to discharge from hospital was about 3 h in all groups. The pain scores in the post‐anaesthetic care unit, mobilization at 24 h and 7 days, and general level of satisfaction were similar between the groups.

Conclusion

The combination of a COX‐2 inhibitor and dexamethasone results in better pain relief 24 h after surgery in patients undergoing outpatient ACL surgery, compared to COX‐2 inhibitor alone or dexamethasone alone. With a dedicated multimodal pain regime, most ACL patients may be discharged within 3 h.
Correlation between cardiac output and reversibility of rocuronium‐induced moderate neuromuscular block with sugammadex
Authors: YOSHIDA F. , SUZUKI T. , KASHIWAI A. , FURUYA T. , KONISHI J. , OGAWA S.
Published: November 2011

Background

The aim of this study was to evaluate the correlation between cardiac output (CO) and reversibility of rocuronium‐induced moderate neuromuscular block with sugammadex in elderly patients.

Methods

Fifty elderly (≥ 65 years) patients were enrolled in this study. During 1.0–1.5% end‐tidal sevoflurane and remifentanil anaesthesia, contraction of the adductor pollicis muscle in response to ulnar nerve stimulation was acceleromyographically quantified. All patients initially received 1 mg/kg rocuronium followed by 0.2 mg/kg whenever the second twitch T2 of the train‐of‐four (TOF) response reappeared. CO was measured throughout the study using a FloTrac™/Vigileo™ monitor. After completion of surgery and at the reappearance of T2, the time required for a bolus dose of 2 mg/kg sugammadex to facilitate recovery to a TOF ratio of 0.9 was recorded, and its correlation with CO was analysed.

Results

Adequate recovery of neuromuscular block was achieved after sugammadex in all patients. Mean CO at the time of reversal with sugammadex was 5.3 l/min (1.3), and recovery time to a TOF ratio of 0.9 was 173.4 s (54.8). A statistically significant inverse correlation was seen between the time to recovery to a TOF ratio of 0.9 and CO [reversal time (s) = −27.7·CO + 298.7, R2
 = 0.461, P < 0.0001].

Conclusions

The time to reach a TOF ratio of 0.9 following sugammadex is dependent on CO in elderly patients.
High‐throughput multiplex PCR genotyping for 35 red blood cell antigens in blood donors
Authors: Jungbauer C. , Hobel C. M. , Schwartz D. W. M. , Mayr W. R.
Published: November 2011

Background and Objectives  One to two per cent of patients in need of red cell transfusion carry irregular antibodies to red blood cell (RBC) antigens and have to be supplied with specially selected blood units. To be able to respond to those requests, blood centres have to screen a significant number of donors for a variety of antigens serologically, which is a costly and through the shortage of reagents, also limited procedure. To make this procedure more efficient, the Austrian Red Cross has developed a genotyping assay as an alternative approach for high throughput RBC typing.

Materials and Methods  A multiplex polymerase chain reaction (PCR) assay was designed for typing 35 RBC antigens in six reaction mixes. The assay includes both common as well as high‐frequency‐alleles:

MNS1, MNS2, MNS3 and MNS4; LU1, LU2, LU8 and LU14; KEL1, KEL2, KEL3, KEL4, KEL6, KEL7, KEL11, KEL17 and KEL21; FY1, FY2, FYBWK and FY0 (FYBES); JK1 and JK2; DI1, DI2, DI3 and DI4; YT1 and YT2; DO1 and DO2; CO1 and CO2; IN1 and IN2.

The assay was validated using 370 selected serologically typed samples. Subsequently 6000 individuals were screened to identify high frequency antigen (HFA)‐negative donors and to facilitate the search for compatible blood for alloimmunized patients.

Results  All controls showed complete concordance for the tested markers. The screening of 6000 donors revealed 57 new HFA‐negative donors and the blood group database was extended by approximately 210 000 results.

Conclusion  The study shows that in practice, this high‐throughput genotyping assay is feasible, fast and provides reliable results. Compared to serological testing, this molecular approach is also very cost‐efficient.
Administration of Prednisolone intravenously or Dexamethason orally in random donors reveals equal results in granulocyte collection: a single centre experience
Authors: Kolovratova V. , List J. , Worel N. , Jilma P. , Leitner G.
Published: November 2011

Since cytokine – mobilization for granulocyte collections in random donors – is not licensed in Austria, we investigated in a prospective analysis the effects of prednisolone or dexamethasone (DXM) in 153 donors (35 women/118 men) and in the collected products. Either prednisolone (50 mg) intravenously 4 h before granulocyte collection or DXM (8 mg) orally 12 h before collection was given. Collections were performed with the Cobe Spectra (CardianBCT, Lakewood). We recorded a significantly higher percentage of granulocytes in the peripheral blood of the DXM. However, the collected number of granulocytes was equal in both groups.
Rural maternity care and health policy: Parents' experiences
Authors: Evans Rebecca , Veitch Craig , Hays Richard , Clark Michele , Larkins Sarah
Published: November 2011

Objective:  To explore rural residents' experiences of access to maternity care with consideration of the policy context.

Design:  This paper describes findings from focus groups with parents which formed part of case study data from a larger study.

Setting:  Four north Queensland rural towns.

Participants:  Thirty‐three parents living in one of the four rural towns.

Main outcome measures:  Identifying prevalent themes in case studies regarding rural parents' expectations and experiences in accessing maternity care.

Results:  Parents desired a local, safe and consistent maternity service. Removing or downgrading rural services introduced new barriers to care for rural residents: (i) increased financial costs; (ii) family issues; and (iii) safety concerns.

Conclusions:  Although concerns about rural residents' health status and health care access have received significant policy attention for over a decade, many of the problems which prompted these policy initiatives remain today. Current policy approaches should be re‐evaluated in order to improve rural Australians' access to vital health services such as maternity care.
Comparison of manual and digital microvascular density counting of RECK expression in glioma
Authors: Rahmah Nunung Nur , Sakai Keiichi , Li Yuhui , Sano Kenji , Hongo Kazuhiro
Published: November 2011

A microvascular density (MVD) counting method for reversion‐inducing cysteine‐rich protein with Kazal motifs (RECK) expression, using a digital image analysis tool, has advantages over manual counting by microscope. Thirty glioma cases with RECK staining were photographed at a magnification of 200× high power field and the photographs in RGB images were analyzed, and stained vessels were captured and were counted automatically. MVD with RECK expression using a digital image analysis tool showed comparable results to those of the manual method. RECK intensity expression could show linear correlation with grades of glioma by the digital method, which was superior compared to the manual method. The present method is recommended to researchers undertaking MVD study for glioma.
Specification and regionalisation of the neural plate border
Authors: Patthey Cédric , Gunhaga Lena
Published: November 2011

During early vertebrate development, the embryonic ectoderm becomes subdivided into neural, neural plate border (border) and epidermal regions. The nervous system is derived from the neural and border domains which, respectively, give rise to the central and peripheral nervous systems. To better understand the functional nervous system we need to know how individual neurons are specified and connected. Our understanding of the early development of the peripheral nervous system has been lagging compared to knowledge regarding central nervous system and epidermal cell lineage decision. Recent advances have shown when and how the specification of border cells is initiated. One important insight is that border specification is already initiated at blastula stages, and can be molecularly and temporally distinguished from rostrocaudal regionalisation of the border. From findings in several species, it is clear that Wnt, Bone Morphogenetic Protein and Fibroblast Growth Factor signals play important roles during the specification and regionalisation of the border. In this review, we highlight the individual roles of these signals and compare models of border specification, including a new model that describes how temporal coordination and epistatic interactions of extracellular signals result in the specification and regionalisation of border cells.
Postnatal differentiation of cortical interneuron signalling
Authors: Sauer Jonas‐Frederic , Bartos Marlene
Published: November 2011

Most GABAergic interneurons in the cortex are born at embryonic stages in the ganglionic eminences and migrate tangentially to their final destination. They continue, however, to differentiate and functionally integrate in the circuitry until later postnatal stages of the rodent brain. Recent investigations show that interneurons undergo marked changes in their morphological, intrinsic and synaptic properties as they mature. Action potential shape and its propagation, the period of transmitter release and the time course of the postsynaptic GABAA receptor‐mediated conductance become faster during the first three to four postnatal weeks, resulting in a developmental switch of interneurons from slow to fast signalling units. At the same time, the nature of GABAergic signalling is classically considered to shift from depolarizing to hyperpolarizing. However, recent studies oppose this view as interneuron synapses can be shunting, excitatory or hyperpolarizing in the mature cortex, demonstrating the coexistence of diverse developmental rules for the emerging effects of GABAergic synapses. Thus, mature interneuron signalling comes in many forms and is apparently optimized to the network in which the neurons are embedded.
Electrical activity patterns and the functional maturation of the neocortex
Authors: Kilb Werner , Kirischuk Sergei , Luhmann Heiko J.
Published: November 2011

At the earliest developmental stages, sensory neocortical areas in various species reveal distinct patterns of spontaneous neuronal network activity. These activity patterns either propagate over large neocortical areas or synchronize local neuronal ensembles. In vitro and in vivo experiments indicate that these spontaneous activity patterns are generated from neuronal networks in the cerebral cortex, in subcortical structures or in the sensory periphery (retina, cochlea, whiskers). At early stages spontaneous periphery‐driven and also sensory evoked activity is relayed to the developing cerebral cortex via the thalamus and the neocortical subplate, which amplifies the afferent sensory input. These early local and large‐scale neuronal activity patterns influence a variety of developmental processes during corticogenesis, such as neurogenesis, apoptosis, neuronal migration, differentiation and network formation. The experimental data also indicate that disturbances in early neuronal patterns may have an impact on the development of cortical layers, columns and networks. In this article we review our current knowledge on the origin of early electrical activity patterns in neocortical sensory areas and their functional implications on shaping developing cortical networks.
Dependence on the transcription factor Shox2 for specification of sensory neurons conveying discriminative touch
Authors: Abdo Hind , Li Lili , Lallemend Francois , Bachy Isabelle , Xu Xiao‐Jun , Rice Frank L. , Ernfors Patrik
Published: November 2011

Touch sensation is mediated by specific subtypes of sensory neurons which develop in a hierarchical process from common early progenitor neurons, but the molecular mechanism that underlies diversification of touch‐sensitive mechanoreceptive neurons is not fully known. Here, we use genetically manipulated mice to examine whether the transcription factor short stature homeobox 2 (Shox2) participates in the acquisition of neuronal subtypes conveying touch sensation. We show that Shox2 encodes the development of category I low‐threshold mechanoreceptive neurons in glabrous skin, i.e. discriminative touch‐sensitive neurons which form innervations of epidermal Merkel cell and Meissner corpuscles. In contrast, other sensory fiber endings, including those innervating Pacinian corpuscles, are not dependent on Shox2. Shox2 is expressed in neurons of most or all classes of sensory neurons at early embryonic stages and is later confined to touch‐sensitive neurons expressing Ret and/or TrkB. Conditional deletion of Shox2 and analysis of Runx3−/−;Bax−/− mutant mice reveals that Runx3 is suppressing Shox2 while Shox2 is necessary for TrkB expression, and that these interactions are necessary for diversification of TrkB+ and TrkC+ mechanoreceptive neurons. In particular, development of TrkB+/Ret+ and TrkB+/Ret− touch‐sensitive neurons is critically dependent on Shox2. Consistently, Shox2 conditional mutant mice demonstrate a dramatic impairment of light touch responses. These results show that Shox2 is required for specification of a subclass of TrkB+ sensory neurons which convey the sensation of discriminative touch arising from stimuli of the skin.
Differential gene expression in migratory streams of cortical interneurons
Authors: Antypa Mary , Faux Clare , Eichele Gregor , Parnavelas John G. , Andrews William D.
Published: November 2011

Cortical interneurons originate in the ganglionic eminences of the subpallium and migrate into the cortex in well‐defined tangential streams. At the start of corticogenesis, two streams of migrating neurons are evident: a superficial one at the level of the preplate (PPL), and a deeper one at the level of the intermediate zone (IZ). Currently, little is known about the signalling mechanisms that regulate interneuron migration, and almost nothing is known about the molecules that may be involved in their choice of migratory stream. Here, we performed a microarray analysis, comparing the changes in gene expression between cells migrating in the PPL and those migrating in the IZ at embryonic day 13.5. This analysis identified genes, many of them novel, that were upregulated in one of the two streams. Moreover, polymerase chain reaction, in situ hybridization experiments and immunohistochemistry showed the expression of these genes in interneurons migrating within the PPL or IZ, suggesting that they play a role in their migration and choice of stream.
Bidirectional pattern‐specific plasticity of the slow afterhyperpolarization in rats: role for high‐voltage activated Ca2+ channels and Ih
Authors: Kaczorowski C. C.
Published: November 2011

A burst of action potentials in hippocampal neurons is followed by a slow afterhyperpolarization (sAHP) that serves to limit subsequent firing. A reduction in the sAHP accompanies acquisition of several types of learning, whereas increases in the sAHP are correlated with cognitive impairment. The present study demonstrates in vitro that activity‐dependent bidirectional plasticity of the sAHP does not require synaptic activation, and depends on the pattern of action potential firing. Whole‐cell current‐clamp recordings from CA1 pyramidal neurons in hippocampal slices from young rats (postnatal days14–24) were performed in blockers of synaptic transmission. The sAHP was evoked by action potential firing at gamma‐related (50 Hz, gamma‐AHP) or theta frequencies (5 Hz, theta‐AHP), two firing frequencies implicated in attention and memory. Interestingly, when the gamma‐AHP and theta‐AHP were evoked in the same cell, a gradual potentiation of the gamma‐AHP (186 ± 31%) was observed that was blocked using Ca2+ channel blockers nimodipine (10 μm) or ω‐conotoxin MVIIC (1 μm). In experiments that exclusively evoked the sAHP with 50 Hz firing, the gamma‐AHP was similarly potentiated (198 ± 44%). However, theta‐burst firing pattern alone resulted in a decrease (65 ± 19%) of the sAHP. In these experiments, application of the h‐channel blocker ZD7288 (25 μm) selectively prevented enhancement of the gamma‐AHP. These data demonstrate that induction requirements for bidirectional AHP plasticity depend on the pattern of action potential firing, and result from distinct mechanisms. The identification of novel mechanisms underlying AHP plasticity in vitro provides additional insight into the dynamic processes that may regulate neuronal excitability during learning in vivo.
Development of raphe serotonin neurons from specification to guidance
Authors: Kiyasova Vera , Gaspar Patricia
Published: November 2011

The main features of the development of the serotonin (5‐HT) raphe neurons have been known for many years but more recent molecular studies, using mouse genetics, have since unveiled several intriguing aspects of the specification of the raphe serotonergic system. These studies indicated that, although all 5‐HT neurons in the raphe follow the same general program for their specification, there are also clear regional differences in the way that these neurons are specified and are guided towards different brain targets. Here we overview recent progress made in the understanding of the developmental programming of serotonergic neurons in the mouse raphe, emphasizing data showing how heterogeneous subsets of 5‐HT neurons may be generated. Serotonergic progenitors are produced in the brainstem in different rhombomeres under the influence of a set of secreted factors, sonic hedgehog and fibroblast growth factors, which determine their position in the neural tube. Two main transcriptional gene networks are involved in the specification of 5‐HT identity, with Lmx1b and Pet1 transcription factors as main players. A differential requirement for Pet1 was, however, revealed, which underlies an anatomical and functional diversity. Transcriptional programs controlling 5‐HT identity could also impact axon guidance mechanisms directing 5‐HT neurons to their targets. Although no direct links have yet been established, a large set of molecular determinants have already been shown to be involved in the growth, axon guidance and targeting of 5‐HT raphe neurons, particularly within the forebrain. Alterations in the molecular mechanisms involved in 5‐HT development are likely to have significant roles in mood disease predisposition.
Do brain responses to emotional images and cigarette cues differ? An fMRI study in smokers
Authors: Versace Francesco , Engelmann Jeffrey M. , Jackson Edward F. , Costa Vincent D. , Robinson Jason D. , Lam Cho Y. , Minnix Jennifer A. , Brown Victoria L. , Wetter David W. , Cinciripini Paul M.
Published: November 2011

Chronic smoking is thought to cause changes in brain reward systems that result in overvaluation of cigarette‐related stimuli and undervaluation of natural rewards. We tested the hypotheses that, in smokers, brain circuits involved in emotional processing: (i) would be more active during exposure to cigarette‐related than neutral pictures; and (ii) would be less active to pleasant compared with cigarette‐related pictures, suggesting a devaluation of intrinsically pleasant stimuli. We obtained whole‐brain blood oxygenation level‐dependent (BOLD) functional magnetic resonance imaging data from 35 smokers during the presentation of pleasant (erotica and romance), unpleasant (mutilations and sad), neutral, and cigarette‐related pictures. Whole‐brain analyses showed significantly larger BOLD responses during presentation of cigarette‐related pictures relative to neutral ones within the secondary visual areas, the cingulate gyrus, the frontal gyrus, the dorsal striatum, and the left insula. BOLD responses to erotic pictures exceeded responses to cigarette‐related pictures in all clusters except the insula. Within the left insula we observed larger BOLD responses to cigarette‐related pictures than to all other picture categories. By including intrinsically pleasant and unpleasant pictures in addition to neutral ones, we were able to conclude that the presentation of cigarette‐related pictures activates brain areas supporting emotional processes, but we did not find evidence of overall reduced activation of the brain reward systems in the presence of intrinsically pleasant stimuli.
An audit of anesthetic management and complications of tracheo‐esophageal fistula and esophageal atresia repair
Authors: Knottenbelt Graham , Costi David , Stephens Philip , Beringer Richard , Davidson Andrew
Published: November 2011

Background:  Many different anesthetic techniques have been suggested for the management of tracheo‐oesophageal fistula/oesophageal atresia (TOF/OA) although the incidence of ventilation difficulty is not well known and it is unclear which technique is best in managing this. The aim of our audit was to determine the incidence of ventilation difficulty during repair of TOF/OA. We also recorded the current practice for anesthesia and analgesia in these children as well as the incidence of comorbidities and surgical complications.

Methods:  We retrospectively audited cases of TOF/OA repair over a 3‐year period in four hospitals, recording demographics, comorbidities, surgical data, postoperative complications, and anesthetic technique, including ventilation difficulty and management strategy.

Results:  A total of 111 patients were identified with TOF/OA, and 106 patient notes and 101 anesthetic records were found. 42% of patients were premature, and 57.5% had significant comorbidities. Death was most likely in infants with low birth weight and low gestational age at birth and in those with major cardiac comorbidity. A range of techniques were used for induction, maintenance, extubation, and pain control. There were ventilation difficulties recorded at induction in seven patients, and significant desaturations were recorded in 15 patients intraoperatively.

Conclusions:  This audit adds to the data already published about incidences of complications and comorbidities associated with TOF/OA repair. Defining anesthetic practice with regard to ventilation and analgesic strategies is important in comparing the adequacy and risk of techniques used. Our audit shows that a range of differing anesthetic techniques are still employed by different anesthetists and institutions and details some of the techniques being used for managing difficult ventilation.
Anesthetic and perioperative risk in the patient with Ataxia‐Telangiectasia
Authors: Lockman Justin L. , Iskander Andrew J. , Bembea Melania , Crawford Thomas O. , Lederman Howard M. , McGrath‐Morrow Sharon , Easley R. Blaine
Published: November 2011

Objectives/Aim:  To report our relatively large experience with perioperative care for patients with Ataxia‐Telangiectasia (A‐T) and to identify the nature and frequency of complications.

Background:  Ataxia‐Telangiectasia is a rare autosomal recessive genetic disorder resulting in progressive multisystem degeneration and characteristic findings including complex neurodegeneration, immunodeficiency, increased risk of malignancy, and lung disease. Anecdotal reports have suggested high perioperative morbidity in patients with A‐T, but few data exist.

Methods/Materials:  The Ataxia‐Telangiectasia Clinical Center database was cross‐referenced with operative records between 1995 and 2009 to identify patients with perioperative A‐T, and medical records were reviewed for preoperative history, management techniques, and complications.

Results:  Twenty‐one patients with A‐T underwent 34 anesthetics during the study period. The median age was 12.5 years (range 6–33 years). Common comorbidities included neurologic (100%), pulmonary (68%), immunologic (50%), oncologic (47%), and gastroenterologic (35%) disorders. Supplemental oxygen was required on postanesthesia care unit discharge for 24% of patients with a maximal duration of 24 h. Although mild postoperative hypothermia was relatively common (44% of anesthetics), there were no major complications, no unplanned admissions, and no mortality in this series.

Conclusions:  Although limited by its retrospective nature, this is the first series describing perioperative risk for patients with A‐T. Our results indicate that general anesthesia, airway manipulation, and perioperative mechanical ventilation may be tolerated with only minor postoperative anesthetic concerns. Perioperative providers should be aware of the complex multisystem medical concerns that may arise in these patients.
A giant cell surface protein in Synechococcus WH8102 inhibits feeding by a dinoflagellate predator
Authors: Strom Suzanne L. , Brahamsha Bianca , Fredrickson Kerri A. , Apple Jude K. , Rodríguez Andres Gutiérrez
Published: November 2011

Diverse strains of the marine planktonic cyanobacterium Synechococcus sp. show consistent differences in their susceptibility to predation. We used mutants of Sargasso Sea strain WH8102 (clade III) to test the hypothesis that cell surface proteins play a role in defence against predation by protists. Predation rates by the heterotrophic dinoflagellate Oxyrrhis marina on mutants lacking the giant SwmB protein were always higher (by 1.6 to 3.9×) than those on wild‐type WH8102 cells, and equalled predation rates on a clade I strain (CC9311). In contrast, absence of the SwmA protein, which comprises the S‐layer (surface layer of the cell envelope that is external to the outer membrane), had no effect on predation by O. marina. Reductions in predation rate were not due to dissolved substances in Synechococcus cultures, and could not be accounted for by variations in cell hydrophobicity. We hypothesize that SwmB defends Synechococcus WH8102 by interfering with attachment of dinoflagellate prey capture organelles or cell surface receptors. Giant proteins are predicted in the genomes of multiple Synechococcus isolates, suggesting that this defence strategy may be more general. Strategies for resisting predation will contribute to the differential competitive success of different Synechococcus groups, and to the diversity of natural picophytoplankton assemblages.
Extending the role of Transanal Endoscopic Microsurgery (TEM) in rectal cancer
Authors: Hompes R. , Cunningham C.
Published: November 2011

Increasingly it is becoming clear that there is a role for local excision of early rectal cancer by Transanal Endoscopic Microsurgery (TEM) as part of an organ‐preservation strategy. This role is based on careful preoperative assessment, thorough postoperative histopathological examination and standardized follow up, with recourse to completion or salvage radical surgery in the face of poor prognostic factors, or early concerns over recurrent disease. Additionally, TEM is also proposed in selected circumstances after neoadjuvant treatment for rectal cancer. This latter topic is even more controversial with clinical evidence still evolving, but specialist centres report impressive results that cannot be ignored in the modern management of rectal cancer.
Natural Orifice Transluminal Endoscopic Surgery (NOTES) and colorectal cancer?
Authors: Morino M. , Verra M. , Famiglietti F. , Arezzo A.
Published: November 2011

Surgical techniques and technologies are rapidly evolving. In the field of colorectal surgery the transanal video‐assisted approach was introduced by Buess, 30 years ago, with transanal endoscopic microsurgery (TEM). In more recent years different techniques and technologies have been proposed, including natural orifice specimen extraction (NOSE), natural orifice transluminal endoscopic surgery (NOTES) and single‐access surgery. Furthermore, a better understanding of the prognostic and risk factors of rectal cancer has allowed TEM to expand its indications to local resection of selected tumours, and more recently there have been proposals for sentinel node biopsy in colon and rectal cancer.