Short-term preoperative drainage is associated with improved postoperative outcomes compared to that of long-term biliary drainage in pancreatic surgery.

PURPOSE: The treatment of choice for patients presenting with obstructive cholestasis due to periampullary carcinoma is oncologic resection without preoperative biliary drainage (PBD). However, resection without PBD becomes virtually impossible in patients with obstructive cholangitis or severely impaired liver cell function. The appropriate duration of drainage by PBD has not yet been defined for these patients. METHODS: A retrospective analysis was conducted on 170 patients scheduled for pancreatic resection following biliary drainage between January 2012 and June 2018 at the University Hospital Dresden in Germany. All patients were deemed eligible for inclusion, regardless of the underlying disease entity. The primary endpoint analysis was defined as the overall morbidity (according to the Clavien-Dindo classification). Secondary endpoints were the in-hospital mortality and malignancy adjusted overall and recurrence-free survival rates. RESULTS: A total of 170 patients were included, of which 45 (26.5%) and 125 (73.5%) were assigned to the short-term (< 4 weeks) and long-term (≥ 4 weeks) preoperative drainage groups, respectively. Surgical complications (Clavien-Dindo classification > 2) occurred in 80 (47.1%) patients, with significantly fewer complications observed in the short-term drainage group (31.1% vs. 52%; p = 0.02). We found that long-term preoperative drainage (unadjusted OR, 3.386; 95% CI, 1.507-7.606; p < 0.01) and periampullary carcinoma (unadjusted OR, 5.519; 95% CI, 1.722-17.685; p-value < 0.01) were independent risk factors for postoperative morbidity, based on the results of a multivariate regression model. The adjusted overall and recurrence-free survival did not differ between the groups (p = 0.12). CONCLUSION: PBD in patients scheduled for pancreatic surgery is associated with substantial perioperative morbidity. Our results indicate that patients who have undergone PBD should be operated on within 4 weeks after drainage.

Simple Wound Irrigation in the Postoperative Treatment for Surgically Drained Spontaneous Soft Tissue Abscesses: A Prospective, Randomized Controlled Trial.

BACKGROUND: Soft tissue abscesses are among the most frequently encountered medical problems treated by different surgeons. Standard therapy remains incision and drainage with sterile saline irrigation during postoperative wound healing period. Aim of this prospective randomized controlled trial was to compare sterile irrigation versus nonsterile irrigation. STUDY DESIGN: A single center randomized controlled trial was performed to investigate postoperative wound irrigation. The control group used sterile irrigation, and the intervention group used nonsterile irrigation. Primary endpoints were reinfection and reintervention rates, assessed during follow-up controls for up to 2 years. Secondary endpoints were the duration of wound healing, inability to work, pain and quality of life. RESULTS: Between 04/2016 and 05/2017, 118 patients were randomized into two groups, with 61 allocated to the control- and 57 to the intervention group. Reinfection occurred in a total of 4 cases (6.6%) in the sterile protocol and 4 (7%) in the nonsterile protocol. Quality of life and pain values were comparable during the wound healing period, and patients treated according to the nonsterile irrigation protocol used significantly fewer wound care service teams. Despite equal wound persistence rates, a substantially shorter amount of time off from work was reported in the nonsterile protocol group (p value 0.086). CONCLUSION: This prospective, randomized trial indicates that a nonsterile irrigation protocol for patients operated on for soft tissue abscesses is not inferior to the standard sterile protocol. Moreover, a nonsterile irrigation protocol leads to a shorter period of inability to work with comparable pain and quality of life scores during the wound healing period.

SLC6A2 and SLC6A4 variants interact with venlafaxine serum concentrations to influence therapy outcome.

OBJECTIVE: The effects of genetic variants in genes encoding the target structures of antidepressants on the therapeutic efficacy of antidepressant drugs have been investigated with unconclusive results. One possible confounding factor in most studies was the fact that drug serum concentrations had not been determined. METHODS: Within a clinical setting, 56 inpatients suffering from depressive episodes in the context of either major depressive disorder or bipolar affective disorder were studied. Response to venlafaxine was assessed after 4 weeks of treatment and correlated to serum concentration and functional variants in genes encoding the norepinephrine (SLC6A2; rs28386840) and the serotonin transporter (SLC6A4; [5-HTTLPR], rs25531). Symptom change was evaluated using the Clinical Global Impression-Improvement (CGI-I) scale. RESULTS: No association between therapeutic response, venlafaxine serum concentration (active moiety) and rs28386840 was found. In carriers of the high expressing SLC6A4 genotype (lAlA-), a poor response to venlafaxine was found significantly more often. In subsamples stratified for serum concentration this held true for patients with serum concentrations between 201 and 400 ng/mL (n=21), while in patients with sub- (≤ 200 ng/mL; n=12) and supra-recommended (> 400 ng/mL; n=23) concentrations, no significant differences were observed. DISCUSSION: The observed association is consistent with findings of some previous studies, whereas others showed differing results highlighting the need for further investigations.

Compositional divergence and convergence in arbuscular mycorrhizal fungal communities.

In spite of the controversy that they have generated, neutral models provide ecologists with powerful tools for creating dynamic predictions about beta-diversity in ecological communities. Ecologists can achieve an understanding of the assembly rules operating in nature by noting when and how these predictions are met or not met. This is particularly valuable for those groups of organisms that are challenging to study under natural conditions (e.g., bacteria and fungi). Here, we focused on arbuscular mycorrhizal fungal (AMF) communities and performed an extensive literature search that allowed us to synthesize the information in 19 data sets with the minimal requisites for creating a null hypothesis in terms of community dissimilarity expected under neutral dynamics. In order to achieve this task, we calculated the first estimates of neutral parameters for several AMF communities from different ecosystems. Communities were shown either to be consistent with neutrality or to diverge or converge with respect to the levels of compositional dissimilarity expected under neutrality. These data support the hypothesis that divergence occurs in systems where the effect of limited dispersal is overwhelmed by anthropogenic disturbance or extreme biological and environmental heterogeneity, whereas communities converge when systems have the potential for niche divergence within a relatively homogeneous set of environmental conditions. Regarding the study cases that were consistent with neutrality, the sampling designs employed may have covered relatively homogeneous environments in which the effects of dispersal limitation overwhelmed minor differences among AMF taxa that would lead to environmental filtering. Using neutral models we showed for the first time for a soil microbial group the conditions under which different assembly processes may determine different patterns of beta-diversity. Our synthesis is an important step showing how the application of general ecological theories to a model microbial taxon has the potential to shed light on the assembly and ecological dynamics of communities.

[Highlights of pancreatic surgery: extended indications in pancreatic neuroendocrine tumors]. / Highlights der Pankreaschirurgie: erweiterte Indikationen bei neuroendokrinen Tumoren des Pankreas.

Advanced pancreatic neuroendocrine tumors (paNET) are mostly characterized by infiltration of vascular structures and/or neighboring organs. The indications for resection in these cases should be measured based on the possibility of an R0 resection. Although the data situation for this rare entity is limited, small case series have shown a significant survival advantage in patients who underwent a radical resection in locally advanced stages of paNET. Both vascular reconstruction and multivisceral resection, when performed at experienced centers, should be considered as curative treatment options. The very special biological behavior of the paNET and the often young patient age justify a much more aggressive approach compared to the pancreatic ductal adenocarcinoma.

Inner composition alignment for inferring directed networks from short time series.

Identifying causal links (couplings) is a fundamental problem that facilitates the understanding of emerging structures in complex networks. We propose and analyze inner composition alignment-a novel, permutation-based asymmetric association measure to detect regulatory links from very short time series, currently applied to gene expression. The measure can be used to infer the direction of couplings, detect indirect (superfluous) links, and account for autoregulation. Applications to the gene regulatory network of E. coli are presented.

Perioperative Blood Management of Preoperative Anemia Determines Long-Term Outcome in Patients with Pancreatic Surgery.

BACKGROUND/PURPOSE: Anemia affects the postoperative course of patients undergoing a major surgical procedure. However, it remains unclear whether anemia has a different impact on the long-term outcome of patients with malignant or benign pancreatic disease. METHODS: A retrospective analysis of patients undergoing pancreatic surgery for pancreatic malignancies or chronic pancreatitis was conducted between January 2012 and June 2018 at the University Hospital Dresden, Germany. The occurrence of preoperative anemia and the administration of pre-, intra-, and postoperative blood transfusions were correlated with postoperative complications and survival data by uni- and multivariate analysis. RESULTS: A total of 682 patients were included with 482 (70.7%) undergoing surgical procedures for pancreatic malignancies. Univariate regression analysis confirmed preoperative anemia as a risk factor for postoperative complications > grade 2 according to the Clavien-Dindo classification. Multivariate regression analyses indicated postoperative blood transfusion as an independent risk factor for postoperative complications in patients with a benign (OR 20.5; p value < 0.001) and a malignant pancreatic lesion (OR 4.7; p value < 0.01). Univariate and multivariate analysis revealed preoperative anemia and pre-, intra-, and postoperative blood transfusions as independent prognostic factors for shorter overall survival in benign and malignant patients (p value < 0.001-0.01). CONCLUSION: Preoperative anemia is a prevalent, independent, and adjustable factor in pancreatic surgery, which poses a significant risk for postoperative complications irrespective of the entity of the underlying disease. It should therefore be understood as an adjustable factor rather than an indicator of underlying disease severity.

Complicaciones relacionadas a la contención fija en ortodoncia:"Efecto giro". Revisión Bibliográfica

Las contenciones fijas en ortodoncia han demostrado tener excelentes resultados para la estabilidad y durabilidad del tratamiento. A pesar de esto, se ha observado que existen ciertos movimientos dentarios indeseados totalmente diferentes a una recidiva a su posición inicial previa al tratamiento de ortodoncia. El llamado "efecto giro" es uno de ellos, y se caracteriza por ser una inclinación en sentidos opuestos de los caninos contralaterales, en donde uno presenta una inclinación hacia vestibular y el otro hacia lingual o palatino. Se presenta principalmente en la mandíbula, a pesar de que la contención permanece perfectamente adherida a los dientes. El objetivo de esta revisión bibliográfica es evaluar los distintos factores reportados en la literatura que puedan estar relacionados con la aparición del "efecto giro" y qué tan relevantes pueden ser en su desarrollo. Como conclusión es importante considerar el carácter multifactorial de este tipo de complicaciones, en donde el tipo y calidad del alambre que se utilice para la contención, junto con las características periodontales del paciente demostraron tener cierta participación en la génesis de este, por lo tanto, resulta fundamental concientizar a los pacientes de la importancia de los controles ortodóncicos periódicos posteriores al retiro de los aparatos fijos para monitorear y controlar los resultados oclusales logrados y el estado de los dispositivos de contención instalados.

As contenções fixas em ortodontia têm demonstrado excelentes resultados para a estabilidade e durabilidade do tratamento. Apesar disso, observou-se que existem certos movimentos dentários indesejados totalmente diferentes de uma recorrência à sua posição inicial anterior ao tratamento ortodôntico. O chamado "efeito de torção" é um deles, e se caracteriza por uma inclinação em sentidos opostos dos caninos contralaterais, onde um apresenta uma inclinação para vestibular e outro para lingual ou palatino. Ocorre principalmente na mandíbula, apesar do retentor permanecer perfeitamente preso aos dentes. O objetivo desta revisão bibliográfica é avaliar os diferentes fatores relatados na literatura que podem estar relacionados ao aparecimento do "efeito turn" e quão relevantes podem ser no seu desenvolvimento. Em conclusão, é importante considerar a natureza multifatorial deste tipo de complicações, onde o tipo e a qualidade do fio utilizado para contenção, juntamente com as características periodontais do paciente, mostraram algum envolvimento na sua génese, pelo que é essencial conscientizar os pacientes sobre a importância de check-ups ortodônticos periódicos após a remoção dos aparelhos fixos para monitorar e controlar os resultados oclusais alcançados e o estado dos dispositivos de contenção instalados.

Lipopolysaccharide induces prostaglandin H synthase-2 protein and mRNA in human alveolar macrophages and blood monocytes.

We and others have previously demonstrated that human alveolar macrophages produce more PGE2 in response to lipopolysaccharide (LPS) than do blood monocytes. We hypothesized that this observation was due to a greater increase in prostaglandin H synthase-2 (PGHS-2) enzyme mass in the macrophage compared to the monocyte. To evaluate this hypothesis, alveolar macrophages and blood monocytes were obtained from healthy nonsmoking volunteers. The cells were cultured in the presence of 0 to 10 micrograms/ml LPS. LPS induced the synthesis of large amounts of a new 75-kD protein in human alveolar macrophages, and a lesser amount in monocytes. Synthesis of this protein required more than 6 h and peaked in 24 to 48 h; the protein reacted with an anti-PGHS-2 antibody prepared against mouse PGHS-2. Associated with synthesis of the protein was a marked increase in LPS-stimulated and arachidonic acid-stimulated synthesis of PGE2 by alveolar macrophages compared to monocytes. Cells not exposed to LPS contained only PGHS-1 and synthesized very little PGE2 during culture or in response to exogenous arachidonic acid. An LPS-induced mRNA, which hybridized to a human cDNA probe for PGHS-2 mRNA, was produced in parallel with production of this new protein and was produced in much greater amounts by alveolar macrophages compared to blood monocytes. This mRNA was not detectable in cells not exposed to LPS. In contrast, both types of cells contain mRNA, which hybridizes to a cDNA probe for PGHS-1. This mRNA did not increase in response to LPS. LPS also had no effect on PGHS-1 protein. These data demonstrate that PGE2 synthesis in human alveolar macrophages and blood monocytes correlates to the mass of PGHS-2 in the cell. We conclude that the greater ability of the macrophage to synthesize PGE2 in response to LPS is due to greater synthesis of PGHS-2 by the macrophage.

Diagnostic tests and algorithms used in the investigation of haematuria: systematic reviews and economic evaluation.

OBJECTIVES: To determine the most effective diagnostic strategy for the investigation of microscopic and macroscopic haematuria in adults. DATA SOURCES: Electronic databases from inception to October 2003, updated in August 2004. REVIEW METHODS: A systematic review was undertaken according to published guidelines. Decision analytic modelling was undertaken, based on the findings of the review, expert opinion and additional information from the literature, to assess the relative cost-effectiveness of plausible alternative tests that are part of diagnostic algorithms for haematuria. RESULTS: A total of 118 studies met the inclusion criteria. No studies that evaluated the effectiveness of diagnostic algorithms for haematuria or the effectiveness of screening for haematuria or investigating its underlying cause were identified. Eighteen out of 19 identified studies evaluated dipstick tests and data from these suggested that these are moderately useful in establishing the presence of, but cannot be used to rule out, haematuria. Six studies using haematuria as a test for the presence of a disease indicated that the detection of microhaematuria cannot alone be considered a useful test either to rule in or rule out the presence of a significant underlying pathology (urinary calculi or bladder cancer). Forty-eight of 80 studies addressed methods to localise the source of bleeding (renal or lower urinary tract). The methods and thresholds described in these studies varied greatly, precluding any estimate of a 'best performance' threshold that could be applied across patient groups. However, studies of red blood cell morphology that used a cut-off value of 80% dysmorphic cells for glomerular disease reported consistently high specificities (potentially useful in ruling in a renal cause for haematuria). The reported sensitivities were generally low. Twenty-eight studies included data on the accuracy of laboratory tests (tumour markers, cytology) for the diagnosis of bladder cancer. The majority of tumour marker studies evaluated nuclear matrix protein 22 or bladder tumour antigen. The sensitivity and specificity ranges suggested that neither of these would be useful either for diagnosing bladder cancer or for ruling out patients for further investigation (cystoscopy). However, the evidence remains sparse and the diagnostic accuracy estimates varied widely between studies. Fifteen studies evaluating urine cytology as a test for urinary tract malignancies were heterogeneous and poorly reported. The calculated specificity values were generally high, suggesting some possible utility in confirming malignancy. However, the evidence suggests that urine cytology has no application in ruling out malignancy or excluding patients from further investigation. Fifteen studies evaluated imaging techniques [computed tomography (CT), intravenous urography (IVU) or ultrasound scanning (US)] to detect the underlying cause of haematuria. The target condition and the reference standard varied greatly between these studies. The diagnostic accuracy data for several individual studies appeared promising but meaningful comparison of the available imaging technologies was impossible. Eight studies met the inclusion criteria but addressed different parts of the diagnostic chain (e.g. screening programmes, laboratory investigations, full urological work-up). No single study addressed the complete diagnostic process. The review also highlighted a number of methodological limitations of these studies, including their lack of generalisability to the UK context. Separate decision analytic models were therefore developed to progress estimation of the optimal strategy for the diagnostic management of haematuria. The economic model for the detection of microhaematuria found that immediate microscopy following a positive dipstick test would improve diagnostic efficiency as it eliminates the high number of false positives produced by dipstick testing. Strategies that use routine microscopy may be associated with high numbers of false results, but evidence was lacking regarding the accuracy of routine microscopy and estimates were adopted for the model. The model for imaging the upper urinary tract showed that US detects more tumours than IVU at one-third of the cost, and is also associated with fewer false results. For any cause of haematuria, CT was shown to have a mean incremental cost-effectiveness ratio of pounds sterling 9939 in comparison with the next best option, US. When US is followed up with CT for negative results with persistent haematuria, it dominates the initial use of CT alone, with a saving of pounds sterling 235,000 for the evaluation of 1000 patients. The model for investigation of the lower urinary tract showed that for low-risk patients the use of immediate cystoscopy could be avoided if cystoscopy were used for follow-up patients with a negative initial test using tumour markers and/or cytology, resulting in a saving of pounds sterling 483,000 for the evaluation of 1000 patients. The clinical and economic impact on delayed detection of both upper and lower urinary tract tumours through the use of follow-up testing should be evaluated in future studies. CONCLUSIONS: There are insufficient data currently available to derive an evidence-based algorithm of the diagnostic pathway for haematuria. A hypothetical algorithm based on the opinion and practice of clinical experts in the review team, other published algorithms and the results of economic modelling is presented in this report. This algorithm is presented, for comparative purposes, alongside current US and UK guidelines. The ideas contained in these algorithms and the specific questions outlined should form the basis of future research. Quality assessment of the diagnostic accuracy studies included in this review highlighted several areas of deficiency.

Effect of liver regeneration after partial hepatectomy and ischemia-reperfusion on expression of growth factor receptors.

AIM: To investigate the effects of experimental partial hepatectomy and normothermic ischemia-reperfusion damage on the time course of the expression of four different growth factor receptors in liver regeneration. This is relevant due to the potential therapeutic use of growth factors in stimulating liver regeneration. METHODS: For partial hepatectomy (PH) 80% of the liver mass was resected in Sprague Dawley rats. Ischemia and reperfusion (I/R) were induced by occlusion of the portal vein and the hepatic artery for 15 min. The epidermal growth factor receptor, hepatic growth factor receptor, fibroblast growth factor receptor and tumour necrosis factor receptor-1 were analysed by immunohistochemistry up to 72 h after injury. Quantitative RT-PCR was performed at the time point of minimal receptor expression (24 h). RESULTS: In immunohistochemistry, EGFR, HGFR, FGFR and TNFR1 showed biphasic kinetics after partial hepatectomy with a peak up to 12 h, a nadir after 24 h and another weak increase up to 72 h. During liver regeneration, after ischemia and reperfusion, the receptor expression was lower; the nadir at 24 h after reperfusion was the same. To evaluate whether this nadir was caused by a lack of mRNA transcription, or due to a posttranslational regulation, RT-PCR was performed at 24 h and compared to resting liver. In every probe there was specific mRNA for the receptors. EGFR, FGFR and TNFR1 mRNA expression was equal or lower than in resting liver, HGFR expression after I/R was stronger than in the control. CONCLUSION: At least partially due to a post-transcriptional process, there is a nadir in the expression of the analysed receptors 24 h after liver injury. Therefore, a therapeutic use of growth factors to stimulate liver regeneration 24 h after the damage might be not successful.

Hepatocyte proliferation and apoptosis in rat liver after liver injury.

BACKGROUND/AIMS: In this paper the early phase of proliferate response and apoptosis of hepatocytes after partial liver resection, during reperfusion after ischemia and during sepsis is demonstrated. METHODOLOGY: Experiments were conducted in a rat model with regeneration times of 0.5-24 hours after injury. Proliferation was analyzed by Ki-67 immunohistochemistry and confirmed by double staining with CK18 in FACS. Apoptosis was analyzed by TUNEL technique. RESULTS: Periportal hepatocytes enter the cell cycle already 0.5-2 hours after injury in all three models. This early proliferative response is predominant periportally localized. During reperfusion and during sepsis there was a strict pericentral apoptosis of hepatocytes found. CONCLUSIONS: An early periportal proliferation of hepatocytes is a common reaction of the liver to injury. This proliferation takes place much earlier then the main proliferative response 24-72 h after partial resection. This predominant periportal proliferation together with the pericentral apoptosis fit to the concept of the "streaming liver" in liver regeneration.

Dihydrofluorescein diacetate is superior for detecting intracellular oxidants: comparison with 2',7'-dichlorodihydrofluorescein diacetate, 5(and 6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate, and dihydrorhodamine 123.

To detect intracellular oxidant formation during reoxygenation of anoxic endothelium, the oxidant-sensing fluorescent probes, 2',7'-dichlorodihydrofluorescein diacetate, dihydrorhodamine 123, or 5(and 6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate were added to human umbilical vein endothelial cells during reoxygenation. None of these fluorescent probes were able to differentiate the controls from the reoxygenated cells in the confocal microscope. However, dihydrofluorescein diacetate demonstrated fluorescence of linear structures, consistent with mitochondria, in reoxygenated endothelium. This work tests the hypothesis that dihydrofluorescein diacetate is a better fluorescent probe for detecting intracellular oxidants because it is more reactive toward specific oxidizing species. To investigate this, dihydrofluorescein diacetate was exposed to various oxidizing species (hydrogen peroxide, superoxide [KO2], peroxynitrite, nitric oxide, horseradish peroxidase, ferric iron, xanthine oxidase, cytochrome c, and lipoxygenase) and compared with the three other popular probes. Though oxidized dihydrofluorescein has higher molar fluorescence, comparison of the reactions of dihydrofluorescein with these other three probes in a cell-free system indicates that dihydrofluorescein is sometimes less fluorescent than the other probes. In addition, we find that the reactivity of all of the probes is very complex. Based on the results reported here, it is no longer appropriate to think of these probes as detecting a specific oxidizing species in cells, such as H2O2, but rather as detectors of a broad range of oxidizing reactions that may be increased during intracellular oxidant stress. Cell-loading studies indicate that dihydrofluorescein achieves higher intracellular concentrations than the second brightest intracellular probe, 2',7'-dichlorodihydrofluorescein. This fact and its higher molar fluorescence may account for the superior brightness of dihydrofluorescein diacetate. Dihydrofluorescein diacetate may be a superior fluorescent probe for many cell-based studies.

Chest pain in an aspirin-sensitive asthmatic patient. Eosinophilic esophagitis causing esophageal dysmotility.

We describe a case of eosinophilic esophagitis in a 38-year-old man with aspirin-sensitivity asthma which presented as noncardiac chest pain. Manometric measurements demonstrated tertiary contractions. Biopsies showed a dense eosinophilic infiltrate in the mucosa. There was no response to therapy for reflux. Symptoms quickly resolved with corticosteroid therapy. Subsequent manometric values recorded after corticosteroid therapy showed resolution of the dysmotility. Biopsies showed normal mucosa. Adult asthmatic subjects with noncardiac chest pain should receive further investigation if reflux therapy fails to resolve the symptoms.

Aspergillosis with Aspergillus osteomyelitis and diskitis after heart transplantation: surgical and medical management.

This is the report of a 49-year-old man, who could be cured of aspergillosis with Aspergillus osteomyelitis and diskitis of the lumbar spine by medical and surgical therapy after heart retransplantation. Aspergillus osteomyelitis and diskitis is a rare complication of invasive aspergillosis. Lumbar involvement is the main manifestation, followed by rare locations in the tibia, ribs, wrist, sternum, pelvis, and knee. It is nearly always secondary to pulmonary aspergillosis, which occurs in about 6% to 14% of patients after heart transplantation. For treatment, a combined surgical and medical approach is recommended, which enables quick pain relief for the patient and histologic and microbiologic diagnosis and stabilization of the spine. Because of definitive cure of osteomyelitis cannot be guaranteed by removal of the abscess, medical therapy after surgery is necessary for years.

Criticizing and reassuring oneself: An exploration of forms, styles and reasons in female students.

OBJECTIVES: Self-critical people, compared with those who self-reassure, are at increased risk of psychopathology. However, there has been little work on the different forms and functions of these self-experiences. This study developed two self-report scales to measure forms and functions of self-criticism and self-reassurance and explore their relationship to depression. METHODS: A self-report scale measuring forms of self-criticism and self-reassuring, and a scale measuring possible functions of self-criticism, together with a measure of depression and another self-criticism scale (LOSC), were given to 246 female students. RESULTS: Self-criticizing vs. self-reassuring separated into two components. Forms of self-criticizing separated into two components related to: being self-critical, dwelling on mistakes and sense of inadequacy; and a second component of wanting to hurt the self and feeling self-disgust/hate. The reasons/functions for self-criticism separated into two components. One was related to desires to try to self-improve (called self-improving/correction), and the other to take revenge on, harm or hurt the self for failures (called self-harming/persecuting). Mediation analysis suggested that wanting to harm the self may be particularly pathogenic and is positively mediated by the effects of hating the self and negatively mediated by being able to self-reassure and focus on one's positives. CONCLUSIONS: Self-criticism is not a single process but has different forms, functions, and underpinning emotions. This indicates a need for more detailed research into the variations of self-criticism and the mechanisms for developing self-reassurance.

Contraception concerns.

PIP: The article explains concerns over the changing face of family planning service provision in England. Recent years have witnessed service cutbacks and closure of district health authority family planning clinics at a time of increasing abortion and teenage pregnancy rates. Responding to this service cutback and cessation, consumers have increasingly moved away from services provided in specialist clinics to those offered by general practitioners (GP). The scope and quality of services offered by GPs may, however, fail to equal those available in specialist clinics. Additionally, service seekers, especially youths, may feel uncomfortable communicating with and seeking assistance from health professionals closely known by other family members. Failing to choose family planning exclusively as a career, the GP may also be reticent to provide related advice and services to clients. Training for GPs and practice nurses in both clinical and communications skills is suggested, as are cooperative referral practices between GPs and clinics. Positive signs checking this greater dependence upon GP services include the presence of more attendees at community and hospital family planning clinics in 1989/90, sensitivity to consumer needs among new public health directors, and a slower trend of clinic closings.^ieng

The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia: further evidence and meta-analysis.

NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratio of 1.29 in the meta-analysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia.