Patient-Reported Benefits of Extracranial Venous Therapy: British Columbia CCSVI Registry.
Objective Chronic cerebrospinal venous insufficiency (CCSVI) has been hypothesized to be a risk factor for multiple sclerosis (MS). Venoplasty has been proposed as a treatment for CCSVI. The aim of our study was to gain a better understanding of the "real-world" safety and longitudinal effectiveness of venoplasty Methods: British Columbia residents who self-reported having had venoplasty and consented to participate in the study were interviewed and followed for up to 24 months post-therapy using standardized structured questionnaires Results: Participants reported procedure-related complications (11.5%) and complications within the first month after the procedure (17.3%). Initially, more than 40% of participants perceived that the venoplasty had had positive effects on their health conditions, such as fatigue, numbness, balance, concentration/memory and mobility. However, this improvement was not maintained over time Conclusions: Follow-up patient-reported outcomes indicated that the initial perception of the positive impact of venoplasty on the health conditions of MS patients was not sustained over time. In addition, venoplasty was not without associated morbidity.


'Ovar-Mhc' - ovine major histocompatibility complex: structure and gene polymorphisms.
The major histocompatibility complex (MHC) in sheep, Ovar-Mhc, is poorly characterised, when compared to other domestic animals. However, its basic structure is similar to that of other mammals, comprising class I, II and III regions. Currently, there is evidence for the existence of four class I loci. The class II region is better characterised, with evidence of one DRA, four DRB (one coding and three non-coding), one DQA1, two DQA2, and one each of the DQB1, DQB2, DNA, DOB, DYA, DYB, DMA, and DMB genes in the region. The class III region is the least characterised, with the known presence of complement cascade (C4, C2 and Bf), TNFalpha and CYP21 genes. Products of the class I and II genes, MHC molecules, play a pivotal role in antigen presentation required for eliciting immune responses against invading pathogens. Several studies have focused on polymorphisms of Ovar-Mhc genes and their association with disease resistance. However, more research emphasis is needed on characterising the remaining Ovar-Mhc genes and developing simplified and cost-effective methods to score gene polymorphisms. Haplotype screening, employing multiple markers rather than single genes, would be more meaningful in MHC-disease association studies, as it is well known that most of the MHC loci are tightly linked, exhibiting very little recombination. This review summarises the current knowledge of the structure of Ovar-Mhc and polymorphisms of genes located in the complex.


Interleukin-1 alpha also induces granulocyte-macrophage colony-stimulating factor in immature normal bone marrow cells.
The cytokine interleukin-1 (IL-1) plays a role in the regulation of normal as well as leukemic hematopoiesis. In acute myeloid leukemia (AML), IL-1 induces autocrine granulocyte/macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF) production, and these factors may then synergistically induce proliferation in AML blast cells. In this report, we show that IL-1 stimulates DNA synthesis of highly enriched normal bone marrow blast cells (CD34 positive, adherent cell depleted, CD3/CD14/CD15 negative). The stimulative effect of IL-1 can be blocked with neutralizing anti-TNF alpha and anti-GM-CSF antibodies and, most efficiently, by the combination of anti-TNF alpha and anti-GM-CSF, but not with anti-G-CSF antibody, suggesting that IL-1-induced proliferation was initiated through TNF and GM-CSF release. Concentrations of TNF and GM-CSF increased in the culture medium of normal bone marrow blast cells after IL-1 induction. Of the IL-1-induced cells, 12% were positive for GM-CSF mRNA by in situ hybridization, as opposed to 6% of non-induced cells. Thus, in addition to its effect on leukemic blast cells, IL-1 also acts on normal marrow blast cells. We propose a scheme where IL-1 stimulation of normal bone marrow blast cells leads to the induction of TNF alpha and GM-CSF, which in association stimulate DNA synthesis efficiently according to a paracrine or autocrine mechanism within the marrow blast cell compartment.


Sacral stress fracture in a female field hockey player.
We report a collegiate field hockey player who sustained a sacral fatigue-type stress fracture that manifested as persistent low back and leg pain. The diagnosis of sacral stress fracture was suggested by history and physical examination and confirmed by magnetic resonance imaging. Our patient experienced complete resolution of symptoms after a 3-mo interval of activity restriction. This article describes the first reported case of a sacral stress fracture in a field hockey player.


The tale of two tumours: an undiagnosed case of papillary thyroid carcinoma.
Pituitary metastasis is an infrequent clinical problem occurring in 1%-5% of various autopsy series. Differentiated thyroid carcinoma as the primary malignancy was reported in only 2.1% of the cases. A 53-year-old Filipina presented with 7 months history of progressive loss of vision and headaches. She underwent thyroidectomy 2 years prior to admission for an enlarging neck mass. After then, she was lost to follow-up. Physical examination revealed visual field loss, galactorrhea and a 3×4 cm firm suprasternal mass. Imaging showed a 4.5×5×5 cm mass in the sphenoid and ethmoid sinuses with extension into the sella and suprasellar regions. Biopsy of the mass was consistent with papillary thyroid carcinoma, metastatic. For that, she underwent completion thyroidectomy, followed by surgical debulking of the sellar mass. Postoperatively, there was minimal improvement in vision and 13 months after, she is still on constant follow-up in our clinic, and is due for radioiodine therapy.


[Prevalence of parasitic infections in human stool samples from a hospital in Chenzhou City of Hunan Province].
To investigate the prevalence of parasitic infections in human stool samples from a hospital in Chenzhou City, Hunan Province, so as to provide insights into the management of intestinal parasitic diseases. Stool samples were collected from patients admitted to a hospital in Chenzhou City from September 2020 to March 2021, subjected to physiological saline smearing and microscopy for detection of intestinal parasites. The prevalence of parasitic infections and the species of parasites were descriptively analyzed. The overall prevalence of intestinal parasitic infections was 1.61% in the 10 728 stool samples, and there were 3 samples with mixed infections of two parasite species. A total of seven parasite species were identified, including Blastocystis hominis (162 cases, 1.55%), Giardia lamblia (5 cases, 0.05%), Dientamoeba fragilis (5 cases, 0.05%), Endolimax nana (one case, 0.01%), Iodamoeba bütschlii (one case, 0.01%), Strongyloides stercoralis (one case, 0.01%) and Trichomonas hominis (one case, 0.01%). The prevalence of intestinal parasitic infection was significantly higher among women than in men (2.14% vs. 1.25%; χ2 = 13.01, P < 0.01), and a high prevalence rate was seen among patients at ages of 20 to 30 years (2.99%) and 80 years and older (2.86%); however, no age-specific prevalence of intestinal parasitic infection was detected (χ2 = 12.45, P > 0.05). The overall prevalence of intestinal parasitic infection was low among patients admitted to a hospital in Chenzhou City, and gender-specific prevalence was found. Food-borne and opportunistic parasites were predominant intestinal parasites, including B. hominis, G. lamblia and D. fragilis.


[Diverticula of the right colon. The diagnosis and treatment of complications].
Diverticula are localized in the right colon with a rate of 6.7-14% in Western countries. Two types of diverticula have been described in the right colon, on the basis of etiologic and pathological features: multiple diverticula and solitary diverticulum of the caecum. The most common clinical presentation of the right-sided colonic diverticula is an acute inflammatory complication, which is difficult to distinguish from other causes of right iliac fossa pain. A survey of the literature is presented and personal experience relative to 4 cases of acute diverticulitis of the right colon observed over a 10-year period is described. In all the patients the preoperative diagnosis was acute appendicitis. In two cases the poor clinical conditions of the patients were associated with the free perforation of a solitary caecal diverticulum and diffuse faecal peritonitis. A temporary caecostomy was therefore required. In two cases a localized inflammatory mass was found around a perforated solitary diverticulum of the caecum. An ileocaecal resection was performed. The purpose of this study is to emphasize the epidemiological, etiologic and clinical features of right-sided colonic diverticula, and the diagnostic and therapeutic management of their complications.


Arthropathy and proteinuria: nail-patella syndrome revisited.
Nail-patella syndrome (NPS) is a pleiotropic autosomal-dominant disorder due to mutations in the gene LMX1B. It has traditionally been characterized by a tetrad of dermatologic and musculoskeletal abnormalities. However, one of the most serious manifestations of NPS is kidney disease, which may be present in up to 40% of affected individuals. Although diagnosis can be made at birth, it is often missed, presumably due to the rarity of the condition. A 35-year-old female presented to our clinic with history of small joint pain of 6 months duration. In addition she complained of pedal edema off and on for the last 12 years. Prior to her current presentation she had been managed by a local doctor symptomatically. On evaluation, a nephrotic syndrome was obvious, but no secondary cause could be found. However, her physical examination was characteristic of NPS and keeping in view the autosomal dominant nature of the disorder all her three siblings were screened who too showed classical features of NPS. This rare syndrome as a cause of nephrotic range proteinuria is discussed in this report. The report underlines the importance of a good physical examination in a given clinical setting.


Unusual structural trends in the [MCl3([8]aneSe2)](M = As, Sb, Bi) adducts.
The structures of the homologous [MCl(3)([8]aneSe(2))](M = As, Sb or Bi; [8]aneSe(2)= 1,5-diselenacyclooctane) ladder structures formed from planar M(2)Cl(6) units linked by selenoether ligands with trans Se atoms reveal unexpected structural patterns--possible reasons for these are discussed.


Why prudence is needed when interpreting articles reporting clinical trial results in mental health.
Clinical trial results' reliability is impacted by reporting bias. This is primarily manifested as publication bias and outcome reporting bias. Mental health trials are prone to two methodological deficiencies: (1) using small numbers of participants that facilitates false positive findings and exaggerated size effects, and (2) the obligatory use of psychometric scales that require subjective assessments. These two deficiencies contribute to the publication of unreliable results. Considerable reporting bias has been found in safety and efficacy findings in psychotherapy and pharmacotherapy trials. Reporting bias can be carried forward to meta-analyses, a key source for clinical practice guidelines. The final result is the frequent overestimation of treatment effects that could impact patients and clinician-informed decisions. Prospective registration of trials and publication of results are the two major methods to reduce reporting bias. Prospective trial registration will allow checking whether they are published (so it will help to prevent publication bias) and, if published, whether those outcomes and analyses that were deemed as appropriate before trial commencement are actually published (hence helping to find out selective reporting of outcomes). Unfortunately, the rate of registered trials in mental health interventions is low and, frequently, of poor quality. Clinicians should be prudent when interpreting the results of published trials and some meta-analyses - such as those conducted by scientists working for the sponsor company or those that only include published trials. Prescribers, however, should be confident when prescribing drugs following the summary of product characteristics, since regulatory agencies have access to all clinical trial results.


ABCG26-mediated polyketide trafficking and hydroxycinnamoyl spermidines contribute to pollen wall exine formation in Arabidopsis.
Pollen grains are encased by a multilayered, multifunctional wall. The sporopollenin and pollen coat constituents of the outer pollen wall (exine) are contributed by surrounding sporophytic tapetal cells. Because the biosynthesis and development of the exine occurs in the innermost cell layers of the anther, direct observations of this process are difficult. The objective of this study was to investigate the transport and assembly of exine components from tapetal cells to microspores in the intact anthers of Arabidopsis thaliana. Intrinsically fluorescent components of developing tapetum and microspores were imaged in intact, live anthers using two-photon microscopy. Mutants of ABCG26, which encodes an ATP binding cassette transporter required for exine formation, accumulated large fluorescent vacuoles in tapetal cells, with corresponding loss of fluorescence on microspores. These vacuolar inclusions were not observed in tapetal cells of double mutants of abcg26 and genes encoding the proposed sporopollenin polyketide biosynthetic metabolon (ACYL COENZYME A SYNTHETASE5, POLYKETIDE SYNTHASE A [PKSA], PKSB, and TETRAKETIDE α-PYRONE REDUCTASE1), providing a genetic link between transport by ABCG26 and polyketide biosynthesis. Genetic analysis also showed that hydroxycinnamoyl spermidines, known components of the pollen coat, were exported from tapeta prior to programmed cell death in the absence of polyketides, raising the possibility that they are incorporated into the exine prior to pollen coat deposition. We propose a model where ABCG26-exported polyketides traffic from tapetal cells to form the sporopollenin backbone, in coordination with the trafficking of additional constituents, prior to tapetum programmed cell death.


Novel acyloxy derivatives of branched mono- and polyol esters of sal fat: multiviscosity grade lubricant base stocks.
Sal fat, a nontraditional seed oil, was chemically modified to obtain base stocks with a wide range of specifications that can replace mineral oil base stocks. Sal fatty acids were enriched to 72.6% unsaturation using urea adduct method and reacted with branched mono alcohol, 2-ethylhexanol (2-EtH), and polyols namely neopentyl glycol (NPG) and trimethylolpropane (TMP) to obtain corresponding esters. The esters were hydroxylated and then acylated using propionic, butyric, and hexanoic anhydrides to obtain corresponding acylated derivatives. The acylated TMP esters exhibited very high viscosities (427.35-471.93 cSt at 40 °C) similar to those of BS 150 mineral oil base stock range, ISO VG 460, while the acylated NPG esters (268.81-318.84 cSt at 40 °C) and 2-EtH esters viscosities (20.94-24.44 cSt at 40 °C) exhibited viscosities in the range of ISO VG 320 and 22 respectively with good viscosity indices. Acylated NPG esters were found suitable for high temperature and acylated 2-ethylhexyl esters for low viscosity grade industrial applications. It was observed that the thermo-oxidative stabilities of all acylated products were found better compared to other vegetable oil based base stocks. Overall, all the sal fat based lubricant base stocks are promising candidates with a wide range of properties, which can replace most of the mineral oil base stocks with appropriate formulations.


Biotechnological Interventions in Tomato (Solanum lycopersicum) for Drought Stress Tolerance: Achievements and Future Prospects.
Tomato production is severely affected by abiotic stresses (drought, flood, heat, and salt) and causes approximately 70% loss in yield depending on severity and duration of the stress. Drought is the most destructive abiotic stress and tomato is very sensitive to the drought stress, as cultivated tomato lack novel gene(s) for drought stress tolerance. Only 20% of agricultural land worldwide is irrigated, and only 14.51% of that is well-irrigated, while the rest is rain fed. This scenario makes drought very frequent, which restricts the genetically predetermined yield. Primarily, drought disturbs tomato plant physiology by altering plant-water relation and reactive oxygen species (ROS) generation. Many wild tomato species have drought tolerance gene(s); however, their exploitation is very difficult because of high genetic distance and pre- and post-transcriptional barriers for embryo development. To overcome these issues, biotechnological methods, including transgenic technology and CRISPR-Cas, are used to enhance drought tolerance in tomato. Transgenic technology permitted the exploitation of non-host gene/s. On the other hand, CRISPR-Cas9 technology facilitated the editing of host tomato gene(s) for drought stress tolerance. The present review provides updated information on biotechnological intervention in tomato for drought stress management and sustainable agriculture.


Low dose risperidone attenuates cue-induced but not heroin-induced reinstatement of heroin seeking in an animal model of relapse.
The aim of the present study was to investigate the effects of pretreatment with risperidone on heroin self-administration and heroin-seeking behaviour induced by cues and heroin priming. Rats were trained to self-administer heroin under a fixed ratio 1 schedule for 2 wk and nose-poke responding was extinguished for 10 d, after which reinstatement of drug seeking was induced by conditioned cues or heroin priming. Acute risperidone administration at doses 10-100 μg/kg potently and dose-dependently inhibited reinstatement of conditioned cue-induced heroin seeking; the minimum dose of inhibition was 30 μg/kg. In contrast, risperidone at the same doses did not attenuate reinstatement induced by two priming doses of heroin (100 or 250 μg/kg s.c.). Risperidone at these doses failed to alter heroin self-administration and locomotion activity. These data demonstrate that acute treatment with low-dose risperidone inhibits conditioned cue-induced heroin seeking and risperidone may be an adjunctive therapy for the treatment of heroin addiction.


[Lower back pain in the primary care setting - Non-specific and specific pain].
A systematic survey of the symptoms of back pain in terms of triggering event and onset, nature and the extent of influenceability of the pain (lying or standing, under stress, nocturnal pain, localized percussion tenderness, B- symptoms, etc.), as well as structured clinical examination (segment height, radiance, projection, reflex status, sensitivity and motor function) allows an initial and therefore orienting classification of back pain as non-specific or specific. In the primary care setting many patients can be treated extremely effectively and economically from a cost perspective. In addition to the fastest possible pain relief, it is important to prevent the disease becoming chronic. A wide range of pharmacological treatment can be combined with non-pharmacological measures, such as early on exercises, promoting every day mobility, physiotherapy, manual therapy etc.. 20 % of patients with lower back pain have a determinable cause that needs to be rapidly identified. In addition to laboratory diagnostics, structured morphological imaging is necessary. Causes of specific back pain include: fractures, infections, radiculopathy, tumors, axial spondylarthritis as well as extravertebral causes. In the further cause of treatment, it may be necessary to consult medical specialists in the fields of radiology, orthopedics, neurology, neurosurgery, rheumatology, psychotherapy, psychiatry, among others. Treatment is managed by the primary care provider, who should also receive and re-evaluate all findings during the course of the disease.


Suppressive effect of human interferon on memory cells primed to different HLA-D specificities.
In primed lymphocyte typing (PLT), lymphocytes will respond with accelerated kinetics and increased magnitude when confronted with the same stimulating cells in a secondary MLC, or with other cells sharing their HLA-D determinants. Human lymphoblastoid interferon (HIF) caused a dose-dependent inhibition of 3H-TdR uptake in PLT cultures. Flow cytometry cell cycle analysis of HIF-treated PLT cells has shown reduced number of cells in S phase with a concomitant rise in the number of cells in the G0-G1 phase; this suggests that interferon has blocked the progression of PLT cells into S phase. Also HIF inhibited cells proliferation in response to a third party sharing a common determinant, Dw5 with the primary stimulator cell. HIF may be a potential immuno-suppressive agent for transplantation. The well-known antiviral effect of HIF might also prove useful in prevention opportunistic viral infection during transplantation.


Production of complement components by cells of the immune system.
The complement system is an important part of the innate immune defence. It contributes not only to local inflammation, removal and killing of pathogens, but it also assists in shaping of the adaptive immune response. Besides a role in inflammation, complement is also involved in physiological processes such as waste disposal and developmental programmes. The complement system comprises several soluble and membrane-bound proteins. The bulk of the soluble proteins is produced mainly by the liver. While several complement proteins are produced by a wide variety of cell types, other complement proteins are produced by only a few related cell types. As these data suggest that local production by specific cell types may have specific functions, more detailed studies have been employed recently analysing the local and even intracellular role of these complement proteins. Here we review the current knowledge about extrahepatic production and/or secretion of complement components. More specifically, we address what is known about complement synthesis by cells of the human immune system.


[The relationship between malnutrition and immune].
Malnutrition is the primary cause of immunodeficiency worldwide and profoundly affects immune responses. Malnutrition diminishes immune function and therefore prevents the host from mounting an adequate protective response to infectious agents. In turn, infections alter nutrient status and can create a deficiency state. Thus, malnutrition and infection often act synergistically to increase morbidity and mortality. Almost all forms of immunity may be affected by PEM, but non-specific immune responses and cell-mediated immunity are more severely affected than humoral (antibody) responses. Altered immune functions due to the aging process mainly concern T-cell-mediated immune functions, such as diminished T-cell proliferation, antibody response after immunization with T-cell-dependent antigens, impaired delayed-type hypersensitivity response and IL-2 production, whereas anti-inflammatory cytokines are elevated. These findings indicate a yet unexplained shift from pro-inflammatory Th1 cell response to an anti-inflammatory Th2 response with aging. Aging and simultaneous nutritional deficiency exert a cumulative influence on the immune response. Maintaining optimal nutritional status is therefore crucial for aging in good health.


[The influence of nettle and burdock extracts in combination with different diets on dyslipidemia in diabetes mellitus model].
The influence of low-fat diet, nettle (Urtica dioica) leafs and burdock (Arctium lappa) roots extracts on lipid metabolism and glycosylation reactions has been investigated in experimental diabetes mellitus. These extracts were applied in diets with both high and low fat content. The experiments were performed on 90 noninbred male albino rats (200–220 g) that were divided into 9 experimental groups. Diabetes mellitus was modeled with twice-repeated intraperitoneal streptozotocin (30 mg/kg) injections. The animals received food with increased fat content (proteins – 8%, fats – 30%, carbohydrates – 62% of total daily caloric content) during 4 weeks before streptozotocine injections and 8 weeks after its discontinuation. Simultaneously the rats were daily administered nettle leafs (100 mg/kg), burdock roots (25 mg/kg) extracts or metformin (100 mg/kg) into the stomach during 10 days. During the period of agents introduction half the animals continued to receive food with high fat content, the other half received low fat diet (proteins – 20%, fats – 8%, carbohydrates – 72% of the total daily caloric content). The forth (control) group received low fat food only without extracts or metformin administration. The levels of blood glucose, glycosylated hemoglobin, malonic dialdehyde, lipid and lipoprotein fractions content were measured. It has been shown that after streptozotocine injections and 30% fat diet consumption the blood glucose level increased by 5.3 fold compared to that of the intact animals, the content of atherogenic lipid fractions increased by 2–8.3 fold and the protein glycosylation reactions were intensified by 1.9–2.5 fold. In animals fed with 8% fat diet the blood glucose and malonic dialdehyde content decreased by 1.8–2.3 fold. In this experiment the levels of triglycerides, total cholesterol, cholesterol of nonhigh-density lipoproteins, low-density and very low-density lipoproteins, as well as the cholesterol and protein content of high-density lipoproteins normalized. The low fat food did not cause glycosylation reactions regression. With the administration of nettle, burdock extracts or metformin to animals that continued to receive high fat food the blood glucose, triglycerides, total cholesterol, cholesterol of nonhigh-density lipoproteins, low-density and very low-density lipoproteins levels decreased by l.6–7.l fold as compared to the parameters in streptozotocine diabetes mellitus. Cholesterol and protein content of high-density lipoproteins increased by l.4–3.7 fold. The herbal extracts also prevented malonic dialdehyde formation, high-density lipoproteins and hemoglobin glycosylation. The nettle and burdock extracts more effectively decreased hyperglycemia, hypertriglyceridemia and lipoperoxidation in animals fed with low fat food. Metformin in the experiment with low fat intake decreased the glucose, low-density and very low-density lipoproteins content to a maximal degree and prevented high-density lipoproteins glycosylation.


The Various Roles of Fatty Acids.
Lipids comprise a large group of chemically heterogeneous compounds. The majority have fatty acids (FA) as part of their structure, making these compounds suitable tools to examine processes raging from cellular to macroscopic levels of organization. Among the multiple roles of FA, they have structural functions as constituents of phospholipids which are the "building blocks" of cell membranes; as part of neutral lipids FA serve as storage materials in cells; and FA derivatives are involved in cell signalling. Studies on FA and their metabolism are important in numerous research fields, including biology, bacteriology, ecology, human nutrition and health. Specific FA and their ratios in cellular membranes may be used as biomarkers to enable the identification of organisms, to study adaptation of bacterial cells to toxic compounds and environmental conditions and to disclose food web connections. In this review, we discuss the various roles of FA in prokaryotes and eukaryotes and highlight the application of FA analysis to elucidate ecological mechanisms. We briefly describe FA synthesis; analyse the role of FA as modulators of cell membrane properties and FA ability to store and supply energy to cells; and inspect the role of polyunsaturated FA (PUFA) and the suitability of using FA as biomarkers of organisms.


Cerebello-thalamo-cortical networks predict positive symptom progression in individuals at ultra-high risk for psychosis.
Prospective longitudinal evaluation of adolescents at ultra-high-risk (UHR) for the development of psychosis enables an enriched neurodevelopmental perspective of disease progression in the absence of many of the factors that typically confound research with formally psychotic patients (antipsychotic medications, drug/alcohol dependence). The cerebellum has been linked to cognitive dysfunction and symptom severity in schizophrenia and recent work from our team suggests that it is a promising target for investigation in UHR individuals as well. However, the cerebellum and cerebello-thalamo-cortical networks have not been investigated developmentally or with respect to disease progression in this critical population. Further, to date, the types of longitudinal multimodal connectivity studies that would substantially inform our understanding of this area have not yet been conducted. In the present investigation 26 UHR and 24 healthy control adolescents were administered structured clinical interviews and scanned at baseline and then again at 12-month time points to investigate both functional and structural connectivity development of cerebello-thalamo-cortical networks in conjunction with symptom progression. Our results provide evidence of abnormal functional and structural cerebellar network development in the UHR group. Crucially, we also found that cerebello-thalamo-cortical network development and connectivity at baseline are associated with positive symptom course, suggesting that cerebellar networks may be a biomarker of disease progression. Together, these findings provide support for neurodevelopmental models of psychotic disorders and suggest that the cerebellum and respective networks with the cortex may be especially important for elucidating the pathophysiology of psychosis and highlighting novel treatment targets.


Immigrants, Ethnicity, and Adherence to Secondary Cardiac Prevention Therapy: A Substudy of the ISLAND Trial.
The objective of this study was to evaluate adherence to guideline-recommended cardiac secondary prevention therapies by immigration and ethnicity. We conducted a retrospective substudy of the Interventions Supporting Long-Term Adherence and Decreasing Cardiovascular Events (ISLAND) randomized controlled trial. A cohort of 1642 participants was analyzed. Patients were categorized based on their self-reported immigrant status as being Canadian or foreign born and based on their visual minority status (as European or a visual minority). We used logistic regression to examine associations between these patient characteristics of interest and patient adherence to statin medication 1 year after myocardial infarction (MI) and completion of cardiac rehabilitation, adjusting for age, sex, and comorbidities. The dataset included outcome data on 1049 (64%) Canadian-born patients and 593 (36%) immigrants. There were 347 (21%) who identified as a visual minority. We report a nonsignificant trend in statin adherence 1 year after MI favouring foreign-born participants compared with Canadian-born participants (odds ratio [OR], 1.26; 95% confidence interval [CI], 0.91-1.68). Visual minorities were found to have no significant difference in statin adherence 1 year after MI compared with participants of European ethnicity (OR, 1.04; 95% CI, 0.72-1.51). Neither immigration status (OR, 0.91; 95% CI, 0.72-1.15) nor visual minority status (OR, 0.97; 95% CI, 0.73-1.28) were associated with cardiac rehabilitation completion. Our findings offer limited support that immigrants with > 10 years of Canadian residency exposure experience greater adherence to statins 1 year after MI. Further research is required to better inform our understanding of secondary prevention strategy among immigrant populations.


Identifying the Role of E2 Domains on Alphavirus Neutralization and Protective Immune Responses.
Chikungunya virus (CHIKV) and other alphaviruses are the etiologic agents of numerous diseases in both humans and animals. Despite this, the viral mediators of protective immunity against alphaviruses are poorly understood, highlighted by the lack of a licensed human vaccine for any member of this virus genus. The alphavirus E2, the receptor-binding envelope protein, is considered to be the predominant target of the protective host immune response. Although envelope protein domains have been studied for vaccine and neutralization in flaviviruses, their role in alphaviruses is less characterized. Here, we describe the role of the alphavirus E2 domains in neutralization and protection through the use of chimeric viruses. Four chimeric viruses were constructed in which individual E2 domains of CHIKV were replaced with the corresponding domain from Semliki Forest virus (SFV) (ΔDomA/ΔDomB/ΔDomC/ ΔDomA+B). Vaccination studies in mice (both live and inactivated virus) revealed that domain B was the primary determinant of neutralization. Neutralization studies with CHIKV immune serum from humans were consistent with mouse studies, as ΔDomB was poorly neutralized. Using chimeric viruses, it was determined that the alphavirus E2 domain B was the critical target of neutralizing antibodies in both mice and humans. Therefore, chimeric viruses may have more relevance for vaccine discovery than peptide-based approaches, which only detect linear epitopes. This study provides new insight into the role of alphavirus E2 domains on neutralization determinants and may be useful for the design of novel therapeutic technologies.


Robot-assisted laparoscopic Boari flap ureteral reimplantation.
Creation of a Boari flap is an option for ureteral reimplantation with high transection or stricture of the ureter. The benefits of laparoscopic surgery include decreased blood loss, quicker recovery time, and improved cosmesis. Robot-assisted surgery offers intraoperative advantages, including three-dimensional visualization with magnification and wristed movements with additional degrees of freedom. A 75-year-old woman with a persistent ureteral stricture opted for robot-assisted surgery for definitive management. To optimize the repair with least tension, creation of a Boari flap was chosen intraoperatively. Surgery and recovery were uncomplicated. Robot-assisted laparoscopic surgery can be safely used for Boari flap ureteral reimplantation.


[Syncope and work. STePS study (Short Term Prognosis of Syncope)].
Recurrent syncope is a common medical problem responsible for 3-5% of emergency department (ED) accesses and 1-6% of hospital admissions. If syncope occurs in a subject working in a critical safety task, the consequences of this event might be very dangerous for the worker, colleagues, others or for the environment. Therefore, syncope management is a major problem for occupational medicine, converning the general safety at work. To evaluate the syncope events in a group of potential workers aged 18 to 65 years; to evaluate the symptoms preceding syncope and the presence of associated illnesses and recurrent events. This study is part of the prospective study STePS (Short Term Prognosis of Syncope), and included 305 consecutive patients (aged 18-65 years, female 56%) who had syncope as a main symptom and presented at ED of four general hospitals in the Milan area, Italy, between the 23rd of January and 30th of June 2004. The 24% of subjects were hospitalized. In 21% the syncope occurs suddenly without any preceding symptom. The 67% of subjects didn't have any important illness at the time. 50% of subjects had recurrent syncope. In four subjects another syncope occurred in a 10 day follow-up. occupational medicine should consider syncope scrupulously. Proper diagnostic management is important to permit a correct evaluation of work safety issues.


Lancet Countdown indicators for Italy: tracking progress on climate change and health
to provide evidence of the health impacts of climate change in Italy. descriptive study. the indicators published in the 2022 Lancet Countdown report were adapted and refined to provide the most recent data relevant to Italy. twelve indicators were measured, organized within five sections mirroring those of the 2022 Lancet Countdown report: climate change impacts, exposures, and vulnerabilities; adaptation, planning, and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. the overall picture depicted by the analysis of the 12 indicators reveals two key findings. First, climate change is already affecting the health of Italian populations, with effects not being uniform across the Country and with the most vulnerable groups being disproportionately at risk. Second, results showed that Italy's mitigation response has been partial, with major costs to human health. Accelerated climate change mitigation through energy system decarbonisation and shifts to more sustainable modes of transport could offer major benefits to health from cleaner air locally and from more active lifestyles, and to climate change from reduction of global warming. The decarbonisation of agricultural systems would similarly offer health co-benefits to Italian population. Conclusions: through accelerated action on climate change mitigation, Italy has the opportunity of delivering major and immediate health benefits to its population. Developing a key set of local indicators to monitor the impacts of climate change and evaluate response actions, in terms of adaptation and mitigation, can help support and enhance policy and action to fight climate changes.


Effect of recombinant human interleukin-3 (rhIL-3) on persisting chemotherapy-induced thrombocytopenia.
A 57 year old woman with heavily pretreated advanced vaginal cancer (FIGO III) developed severe thrombocytopenia (7000/microliter) with bleedings after chemotherapy. This patient was treated with recombinant human interleukin-3 (rhIL-3) after 26 platelet transfusions (25 pooled transfusions and one HLA-matched platelet transfusion) had not been effective. Increase of thrombocyte counts began 2 days after rhIL-3 therapy. Side-effects due to rhIL-3 administration (flu-like symptoms) were mild and could be treated effectively with paracetamol and clemastin. These data support first evidence for efficacy of rhIL-3 in chemotherapy-induced thrombocytopenia and may open new perspectives for its clinical application.


Identification of the protease and the turnover signal responsible for cell cycle-dependent degradation of the Caulobacter FliF motor protein.
Flagellar ejection is tightly coupled to the cell cycle in Caulobacter crescentus. The MS ring protein FliF, which anchors the flagellar structure in the inner membrane, is degraded coincident with flagellar release. Previous work showed that removal of 26 amino acids from the C terminus of FliF prevents degradation of the protein and interferes with flagellar assembly. To understand FliF degradation in more detail, we identified the protease responsible for FliF degradation and performed a high-resolution mutational analysis of the C-terminal degradation signal of FliF. Cell cycle-dependent turnover of FliF requires an intact clpA gene, suggesting that the ClpAP protease is required for removal of the MS ring protein. Deletion analysis of the entire C-terminal cytoplasmic portion of FliF C confirmed that the degradation signal was contained in the last 26 amino acids that were identified previously. However, only deletions longer than 20 amino acids led to a stable FliF protein, while shorter deletions dispersed over the entire 26 amino acids critical for turnover had little effect on stability. This indicated that the nature of the degradation signal is not based on a distinct primary amino acid sequence. The addition of charged amino acids to the C-terminal end abolished cell cycle-dependent FliF degradation, implying that a hydrophobic tail feature is important for the degradation of FliF. Consistent with this, ClpA-dependent degradation was restored when a short stretch of hydrophobic amino acids was added to the C terminus of stable FliF mutant forms.


Could the interaction of neuroleptics with calmodulin be an "explanation" of the psychotropic effects?
Calmodulin is a protein with calcium-dependent binding sites. Binding of calcium ions induces changes in the conformation and activation of many enzymes such as adenylate cyclase, guanylate cyclase, ATPase. Neuroleptic drugs bind calmodulin. Trifluoperazine has a very high affinity for calmodulin. Tricyclic antidepressants and benzodiazepines also bind calmodulin. Binding of neuroleptics inhibits many biological phenomena such as lymphocyte endocytosis, platelets aggregation. When neuroleptics are administrated chronically, calmodulin could act in regulation of the receptors specially in the drug induced supersensitivity of striatum dopamine receptors. These experiments about the regulation of the receptors mediated by calmodulin have been performed ten years ago and their results were not confirmed later. Moreover, binding of calmodulin is not specific of neuroleptic drugs. The effects of neuroleptics on calmodulin, only observed in vitro or with animals, seem to be mainly related to structural properties of the drugs.


Pipeline for amplifying and analyzing amplicons of the V1-V3 region of the 16S rRNA gene.
Profiling of 16S rRNA gene sequences is an important tool for testing hypotheses in complex microbial communities, and analysis methods must be updated and validated as sequencing technologies advance. In host-associated bacterial communities, the V1-V3 region of the 16S rRNA gene is a valuable region to profile because it provides a useful level of taxonomic resolution; however, use of Illumina MiSeq data for experiments targeting this region needs validation. Using a MiSeq machine and the version 3 (300 × 2) chemistry, we sequenced the V1-V3 region of the 16S rRNA gene within a mock community. Nineteen bacteria and one archaeon comprised the mock community, and 12 replicate amplifications of the community were performed and sequenced. Sequencing the large fragment (490 bp) that encompasses V1-V3 yielded a higher error rate (3.6 %) than has been reported when using smaller fragment sizes. This higher error rate was due to a large number of sequences that occurred only one or two times among all mock community samples. Removing sequences that occurred one time among all samples (singletons) reduced the error rate to 1.4 %. Diversity estimates of the mock community containing all sequences were inflated, whereas estimates following singleton removal more closely reflected the actual mock community membership. A higher percentage of the sequences could be taxonomically assigned after singleton and doubleton sequences were removed, and the assignments reflected the membership of the input DNA. Sequencing the V1-V3 region of the 16S rRNA gene on the MiSeq platform may require additional sequence curation in silico, and improved error rates and diversity estimates show that removing low-frequency sequences is reasonable. When datasets have a high number of singletons, these singletons can be removed from the analysis without losing statistical power while reducing error and improving microbiota assessment.


Is it more than just constipation?
We report an infant presenting with constipation, whose history and physical examination initiated the investigation that led to the diagnosis of the Currarino triad in the proband and 2 other family members.


[Extracorporeal shock-wave therapy (ESWT) for pseudoarthrosis. A new indication for regional anesthesia].
Extracorporeal shock-wave therapy for the treatment of pseudarthrosis is a new indication for anaesthesia. In a clinical trial of 65 treatments in 53 patients, the anaesthetic procedure is shown. Regional anaesthesia, mainly plexus blocks of the upper and lower extremities, was performed in nearly all cases. The various localisations of the pseudarthroses and the types of anaesthetic techniques used are shown in Table 1. In all, we performed 9 epidural blocks, 2 spinal blocks, 29 axillary blocks, 3 supraclavicular perivascular blocks (Winnie), 1 psoas compartment block, and 20 sciatic/femoral 3-in-1 blocks. The shock waves used for this therapy are several times stronger than those used for nephrolithotripsy. Furthermore, the shockwaves are focused on bone and periosteum, which is abundantly innervated. Therefore, in contrast to nephro-lithotripsy with second-generation lithotripters, anaesthesia must be performed for this therapy. We chose regional anaesthesia for several reasons: the procedures are located in the arms or legs, which can readily be anaesthetised by regional blocks. The duration of treatment ranged up to several hours. By using regional anaesthesia, we were able to avoid unnecessary exposure to general anaesthetics. Finally, most of the patients wanted to stay awake during the new treatment and therefore opted for regional techniques. A typical set-up for the treatment is shown in Fig 1. In 67% of the patients fracture healing was significantly improved by the new therapy. Acceptance of therapy and anaesthesia by the patients was very good.


Left-handedness as a risk factor for fractures.
Left-handedness has been associated with increased fracture risk in a small number of previous studies. This study reports risks for fractures at the proximal humerus, distal forearm, pelvis, foot, and shaft of the tibia/fibula according to handedness in a case-control study conducted from October 1996 to May 2001 among members of Northern California Kaiser Permanente. Handedness was assessed by questionnaire for 2,841 cases and 2,192 controls, and subjects were categorized as left-handed, right-handed, ambidextrous, or forced to switch from the left to the right hand. Compared to right-handedness, left-handedness was most strongly associated with an increased risk for proximal humerus fractures (adjusted odds ratio (OR)=2.00, 95% confidence interval (CI) 1.33 to 3.01) and less definitively with fractures of the distal forearm (adjusted OR=1.28, 95% CI 0.92 to 1.80), foot (adjusted OR=1.17, 95% CI 0.82 to 1.65), and pelvis (adjusted OR=1.40, 95% CI 0.71 to 2.74). Ambidextrous individuals had elevated risks for fractures of the distal forearm (adjusted OR=2.99, 95% CI 1.42 to 6.30), foot (adjusted OR=2.59, 95% CI 1.13 to 5.97), shaft of the tibia/fibula (adjusted OR=3.91, 95% CI 1.01 to 15.17), and proximal humerus (adjusted OR=2.37, 95% CI 0.85 to 6.65) when compared with right-handed individuals. Those individuals forced to use the right hand demonstrated no increased risk for fractures at any site. These results suggest that handedness does influence fracture risk, but the reasons for this increased risk are unclear.


Unlicensed personnel administering medications to older persons living at home: a challenge for social and care services.
Administration of medication to care recipients is delegated to home-care assistants working in the municipal social care, alongside responsibility for providing personal assistance for older people. Home-care assistants have practical administration skills, but lack formal medical knowledge. The aim of this study was to explore how home-care assistants perceive administration of medication to older people living at home, as delegated to them in the context of social care. Four focus groups consisting of 19 home-care assistants were conducted. Data were analysed using qualitative content analysis. According to home-care assistants, health and social care depends on delegation arrangements to function effectively, but in the first place it relieves a burden for district nurses. Even when the delegation had expired, administration of medication continued, placing the statutes of regulation in a subordinate position. There was low awareness among home-care assistants about the content of the statutes of delegation. Accepting delegation to administer medications has become an implicit prerequisite for social care work in the municipality. Accepting the delegation to administer medication was inevitable and routine. In practice, the regulating statute is made subordinate and consequently patient safety can be threatened. The organisation of health and social care relies on the delegation arrangement to meet the needs of a growing number of older home-care recipients. This is a crucial task which management within both the healthcare professions and municipal social care needs to address, to bridge the gap between statutes and practice, to create arenas for mutual collaboration in the care recipients' best interest and to ensure patient safety.


Nutritional composition assessment and antimicrobial activity of Catostylus perezi, jellyfish blooms along the coast of Pakistan: an awareness to avoid food neophobia in Pakistan.
This study highlighted the nutritional importance of Catostylus perezi (an edible jellyfish) in Pakistan; a society where a large proportion of the population suffers from malnutrition, while C. perezi, a blessing of the sea, is wasted or exported. In the present study, the amino acid and fatty acid profiles of the oral arms and umbrella of C. perezi were determined by HPLC. The total amino acid concentration (ΣAA) in the oral arms was 151.19 mg/100g, while in the umbrella it was 100.17 mg/100g. The ratio of total essential amino acids to total non-essential amino acids (TEAA/TNEAA) was 0.72 in the oral arms, while it was 0.70 in the umbrella. Higher amount of ω-3 with lower ratio of ω-6/ω-3 in oral arms (0.52), rather umbrella (ω-6/ω-3 ratio; 0.62). The antimicrobial activity, MIC, MBC, and MFC of the whole body of the edible jellyfish were determined. On the basis of polarity, different solvents were used, e.g. water, methanol, dichloromethane, chloroform, and n-hexane. Among all the extracts, the water extract gave the highest ZOI against C. xerosis (29 mm), while the n-hexane extract gave the lowest ZOI against S. aureus (MRSA) ATCC 33591 (8.20 mm). The water extract of C. perezi had high potential against C. xerosis with the highest AMI and PAI (1.53 and 153, respectively), while the same extract had the highest TAI against E. coli (81.43 mL/g). For fungi/yeast, the methanolic extract had the highest ZOI (29.70 mm) against S. cerevisiae and the lowest MIC/MFC (2.40 µg/mL) against the same pathogen. The n-Hexane extract gave the lowest ZOI (11.10 mm) against P. variotii and the highest MIC/MFC (31.60 µg/mL) against Penicillium sp. Atomic force microscopy (AFM) was used to analyse the disintegrating effect of the extracts (with the highest antimicrobial effect) on the cells of selected Gram-positive, Gram-negative and yeast species. The amino acid and fatty acid profiles and antimicrobial assessment showed that C. perezi has great nutritional importance, so the use of C. perezi as food is highly recommended for the Pakistani community.


Helicobacter pylori eradication and its implications for the future.
It has become evident that at least some strains of Helicobacter pylori are pathogenic for humans. However, H. pylori are highly diverse and at least part of this variation involves characteristics related to pathogenicity. A large amount of evidence suggests that H. pylori infection of humans is ancient, and in general, the interaction is not terribly destructive. However, we should try to understand better the risks associated with infection with particular H. pylori strains, and limit treatment to those situations in which the indications for eradicating H. pylori are clear-cut. It is entirely possible that some H. pylori strains are commensals, and that others are symbionts. Eradicating those infections could ultimately cause more harm than good. It is too early to reach firm conclusions about whether all H. pylori infections need to be eradicated.


Antioxidant enzymes and apoptosis.
The role of antioxidant enzymes can be interpreted in terms of fine tuning of the concentration of reactive oxygen species which are required in the redox regulation of the cell cycle and of programmed cell death. This review summarizes findings from papers published in the last few years which deal with the relation between apoptosis and the two antioxidant enzymes, manganous superoxide dismutase (MnSOD) and catalase. With respect to MnSOD, the literature is much in favor of an inhibitory action in apoptosis. Increased MnSOD activity has been shown to prevent cell death via the receptor-mediated apoptotic pathway as well as cell death via the mitochondrial pathway. The literature on the influence of catalase activity on apoptosis is less consistent. Evidence for both an antiapoptotic and a proapoptotic role of catalase can be found. From the results reviewed here, two schemes for the involvement of MnSOD and catalase in the regulation of apoptosis can be extracted: 1) Both MnSOD and catalase inhibit apoptosis by removing superoxide anion radicals or H2O2, respectively, because these reactive oxygen species are mediators required for the apoptotic program or inhibit a survival pathway. 2) An increase in H2O2 by downregulation or inhibition of catalase activity and/or upregulation of MnSOD activity inhibits apoptosis while a decrease in H2O2 by upregulation of catalase activity and/or downregulation of MnSOD activity supports apoptosis, possibly because of a supportive role of H2O2 in a survival pathway. The data reported so far do not allow for an explanation why some cell models appear to fit the first scheme while the second scheme appears to correctly describe other cell models. The present state of the literature reveals that antioxidant enzymes play a more intricate role in cell physiology than previously assumed.


Clinical significance of Girdin expression detected by immunohistochemistry in non-small cell lung cancer.
Girdin protein has been implicated in cell migration and proliferation control. Previous evidence has confirmed that Girdin is a pivotal protein during cancer progression. To date, no evidence has been identified for the clinical significance of Girdin expression in non-small cell lung cancer (NSCLC). The current study aimed to investigate the expression and clinical significance of Girdin protein in NSCLC. In total, 36 tumor samples were obtained from patients undergoing surgery for NSCLC at The 309th Hospital of Chinese People's Liberation Army (Beijing, China). The protein expression of Girdin was determined by immunohistochemistry analysis and the levels of Girdin protein were significantly higher in tumor samples than in distal normal lung tissue. A significant correlation was identified between Girdin overexpression and blood vessel infiltration of the tumor (P=0.013). Furthermore, analysis found that the Girdin-high phenotype was not associated with higher Ki-67 score. Girdin protein was frequently overexpressed in NSCLC and expression of Girdin was associated with blood vessel infiltration. The results of the present study suggest that Girdin should be considered as a potential marker for the prognosis of NSCLC; however, future studies are required to confirm theses results.


Evaluation of LightCycler as a platform for nucleic acid sequence-based amplification (NASBA) in real-time detection of enteroviruses.
The nucleic acid sequence-based amplification (NASBA) assay has been demonstrated to be more sensitive for detection of enteroviruses (EV) than RT-PCR. Many laboratories, however, do not have a dedicated instrument for the NASBA assay. This study aimed to evaluate the use of the Roche LightCycler as a platform for performing the NASBA assay for detection of EV. A diverse subgenera of EV were used to assess the specificity of the NASBA assay, including coxsackie, echovirus, poliovirus, and other enteroviruses together with related and unrelated viruses, including rhinovirus, respiratory syncytial virus, herpes simplex virus, adenovirus, influenza virus A, and cytomegalovirus. All species of EV tested were successfully detected using NASBA and no cross reactivity with other viruses was observed. Using serial dilutions of EV to assess sensitivity, the NASBA assay was compared to an in-house EV RT-PCR assay. The NASBA assay demonstrated a higher level of sensitivity. Fifty-one clinical samples positive for EV by viral culture were also evaluated. All NASBA results obtained were concordant with viral culture results. This study confirmed that the NASBA assay for the detection of EV could be readily performed on the LightCycler and easily incorporated into the workflow of a diagnostic laboratory equipped with a LightCycler, thereby eliminating the need for additional instrumentation.


Lung clearance index to characterize clinical phenotypes of children and adolescents with cystic fibrosis.
Lung clearance index (LCI) is accepted as an early marker of lung disease in cystic fibrosis (CF), however the utility of LCI to identify subgroups of CF disease in the paediatric age group has never been explored. The aim of the study was to characterize phenotypes of children with CF using LCI as a marker of ventilation inhomogeneity and to investigate whether these phenotypes distinguished patients based on time to pulmonary exacerbation (PE). Data were collected on patients with CF aged < 18 years old, attending the CF Center of Milan during outpatient follow-up visits between October 2014 and September 2019. Cluster analysis using agglomerative nesting hierarchical method was performed to generate distinct phenotypes. Time-to-recurrent event analysis investigated association of phenotypes with PE. We collected 313 multiple breath washout tests on 125 children aged 5.5-16.8 years. Cluster analysis identified two divergent phenotypes in children and adolescents of same age, presenting with almost normal FEV1 but with substantial difference in markers of ventilation inhomogeneity (mean LCI difference of 3.4, 95% Confidence Interval [CI] 2.6-4.2). A less severe phenotype was associated with a lower risk of PE relapse (Hazard Ratio 0.45, 95% CI 0.34-0.62). LCI is useful in clinical practice to characterize distinct phenotypes of children and adolescents with mild/normal FEV1. A less severe phenotype translates into a lower risk of PE relapse.


Stem cell-based cardiac tissue engineering.
Cardiovascular diseases are the leading cause of death worldwide, and cell-based therapies represent a potential cure for patients with cardiac diseases such as myocardial infarction, heart failure, and congenital heart diseases. Towards this goal, cardiac tissue engineering is now being investigated as an approach to support cell-based therapies and enhance their efficacy. This review focuses on the latest research in cardiac tissue engineering based on the use of embryonic, induced pluripotent, or adult stem cells. We describe different strategies such as direct injection of cells and/or biomaterials as well as direct replacement therapies with tissue mimics. In this regard, the latest research has shown promising results demonstrating the improvement of cardiac function with different strategies. It is clear from recent studies that the most important consideration to be addressed by new therapeutic strategies is long-term functional improvement. For this goal to be realized, novel and efficient methods of cell delivery are required that enable high cell retention, followed by electrical integration and mechanical coupling of the injected cells or the engineered tissue to the host myocardium.


Micro-Raman spectroscopy used to identify and grade human skin pilomatrixoma.
Raman microspectroscopy was applied to analyze the changes in structural conformation and chemical composition of the mass of human skin pilomatrixoma (PMX). The normal skin dermis, collagen type I, and hydroxyapatite (HA) were used as control. The excised specimens from two patients diagnosed as a typical PMX were detected, in which one specimen was a soft mass, but the other was a hard mass with somewhat calcified deposits via histopathological examination. The Raman spectrum of normal skin dermis was found to be similar to the Raman spectrum of collagen type I, confirming that the collagen type I was a predominant component in normal skin dermis. The differences of Raman peak intensity between normal skin dermis and soft or hard PMX mass were obvious at 1,622-1,558, 1,400-1,230, 1,128, 1,000-850, 749, and 509 cm(-1). In particular, the peak at 1,665 cm(-1) assigned to amide I band shifted to 1,655 cm(-1) and the peak at 1,246 cm(-1) corresponding to amide III band was reduced in its intensity in hard PMX mass. The significant changes in collagen content and its structural conformation, the higher content of tryptophan, and disulfide formation in PMX masses were markedly evidenced. In addition, the shoulder and weak peak at 960 cm(-1) assigned to the stretching vibration of PO(4) (3-) of HA also appeared respectively in the Raman spectra of soft and hard PMX masses, suggesting the occurrence of calcification of HA in the PMX tissue, particularly in the hard PMX mass. The result indicates that the micro-Raman spectroscopy may provide a highly sensitive and specific method for identifying normal skin dermis and how it differs in chemical composition from different PMX tissues.


Combination vitamin D therapy in stage 5 chronic kidney disease.
To review the data supporting combination therapy with vitamin D and vitamin D receptor activators (VDRAs) in patients with stage 5 chronic kidney disease (CKD). Literature was searched using PubMed and EMBASE using the terms kidney disease, kidney failure-chronic, and vitamin D. Limits applied included humans, adults (19 years or older), and clinical trials (and related), with publication dates between January 1, 1980, and May 16, 2011. All English-language publications were analyzed for relevance. Studies appropriate to the objective were evaluated, including 3 prospective observational studies, 1 prospective cohort study, and 1 retrospective study. To our knowledge, there have been no randomized controlled trials evaluating the safety and efficacy of vitamin D supplementation in combination with VDRA therapy in patients with stage 5 CKD. Relatively small observational studies have demonstrated improvements in 25-hydroxyvitamin D (25-OHD) concentrations and markers of mineral and bone metabolism as well as reduced VDRA use in patients with stage 5 CKD. Not all patients in these studies were receiving VDRA therapy. Therapy was safe, with no patients exceeding the recommended upper limit for 25-OHD concentrations and only a small percentage experiencing transient/correctable hypercalcemia. Vitamin D supplementation to maintain 25-OHD concentrations at 20-30 ng/mL or higher with or without VDRA therapy is inexpensive, appears safe, and may have additional health benefits in patients with stage 5 CKD. Well-designed, randomized controlled trials are needed to determine the efficacy and safety of combination vitamin D therapy in patients with stage 5 CKD.


Clinical and hematobiochemical response in canine monocytic ehrlichiosis seropositive dogs of Punjab.
As in India especially, the Punjab state sero-prevalence and distribution of ehrlichiosis in relation to clinico-hematobiochemical response remains largely unexplored. Thus, this study was designed to determine the prevalence of vector (tick)-borne tropical canine pancytopenia caused by Ehrlichia canis through enzyme labeled ImmunoComb® (IC) assay in dogs from in and around Ludhiana, Punjab. Correlation of prevalence was made with various clinico-hematobiochemical parameters. Seroprevalence study was carried out using IC® test kit (Biogal, Galed Labs). The study was conducted in 84 dogs presented to the Small Animal Clinics, Teaching Veterinary Clinical Complex, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab. Out of 84 suspected dogs for ehrlichiosis, based on peripheral thin blood smear examination 12 (14.28%) cases were positive for the morulae of E. canis and 73 (86.90%) dogs were found positive to E. canis antibodies through IC® canine Ehrlichia antibody test kit, respectively. Among the different age groups 1-3 years of aged group showed highest prevalence (41.09%), followed by the 3-6 years age group (32.87%), infection levels were lower in the <1 year of age group dogs (13.69%) and more than 6 years age group dogs (12.32%). The highest prevalence was seen in Labrador retriever. This study indicates that season plays a very important role in the prevalence of ehrlichiosis. The most common findings observed were anemia, leukocytosis, neutropenia, lymphopenia, thrombocytopenia, eosinophilia followed by hyperbilirubinemia, increased levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase, hypoalbuminemia, hyperglobulinaemia, decrease in albumin and globulin ratio, increase in blood urea nitrogen and creatinine. Serological techniques like IC® are more useful for detecting chronic and subclinical infections and are ideally suited to epidemiological investigations.


Carcinoma of the appendix and its natural history in relation to surgical management. A case report.
There are several classifications of appendicular epithelial cancer with a wide variety of nomenclature. Epithelial tumours of the appendix have been classified into four distinct types: carcinoids, mucinous adenocarcinoma (often called mucinous cystadenocarcinoma or malignant mucocele), colonic-type adenocarcinoma, and adenocarcinoids with a dual cell origin. We report a case of a woman who presented to our emergency unit with a history of acute appendicitis and who had undergone an appendectomy. The histopathological analysis showed the presence of a well differentiated mucinous adenocarcinoma, infiltrating the full thickness of the appendix wall.


Phytochemicals reverse P-glycoprotein mediated multidrug resistance via signal transduction pathways.
P-glycoprotein, encoded by ATP-binding cassette transporters B1 gene (ABCB1), renders multidrug resistance (MDR) during cancer chemotherapy. Several synthetic small molecule inhibitors affect P-glycoprotein (P-gp) transport function in MDR tumor cells. However, inhibition of P-gp transport function adversely accumulates chemotherapeutic drugs in non-target normal tissues. Moreover, most small-molecule P-gp inhibitors failed in the clinical trials due to the low therapeutic window at the maximum tolerated dose. Therefore, downregulation of ABCB1-gene expression (P-gp) in tumor tissues seems to be a novel approach rather than inhibiting its transport function for the reversal of multidrug resistance (MDR). Several plant-derived phytochemicals modulate various signal transduction pathways and inhibit translocation of transcription factors, thereby reverses P-gp mediated MDR in tumor cells. Therefore, phytochemicals may be considered an alternative to synthetic small molecule P-gp inhibitors for the reversal of MDR in cancer cells. This review discussed the role of natural phytochemicals that modulate ABCB1 expression through various signal transduction pathways in MDR cancer cells. Therefore, modulating the cell signaling pathways by phytochemicals might play crucial roles in modulating ABCB1 gene expression and the reversal of MDR.


Measuring and interpreting the predictive validity of violence risk assessments: an overview of the special issue.
Mental health professionals are routinely called upon to assess and testify concerning the violence risk of their patients. Expert opinion on risk assessment continues to influence decisions resulting in the long-term denial of civil liberty or even death in the case of capital proceedings. Today, many clinicians use structured risk assessment tools to assist in these tasks. Although few would claim that violence can be predicted without error, all but the most skeptical would concede that our knowledge and ability to assess violence risk far exceeds that of three decades ago. This said, whether current practices are empirically, ethically, or legally valid remains a question of great importance given the consequences that may follow erroneous assessments. And while 30 years ago there was a broad (albeit often overstated) consensus that expert opinion on this topic was inherently suspect, today the field appears to operate on a broad (albeit often overstated) consensus that practices have improved to a sufficient extent to warrant the sizeable impact that violence risk assessments often have on individual liberty, levels of service, and resource allocation.


Roles of vimentin and 14-3-3 zeta/delta in the inhibitory effects of heparin on PC-3M cell proliferation and B16-F10-luc-G5 cells metastasis.
To investigate the inhibitory effects of heparin on PC-3M cells proliferation in vitro and B16-F10-luc-G5 cells metastasis in Balb/c nude mice and identify the protein expression patterns to elucidate the action mechanism of heparin. Human prostate cancer PC-3M cells were incubated with heparin 0.5 to 125 μg/mL for 24 h. The proliferation of PC-3M cells was assessed by MTS assay. BrdU incoporation and Ki67 expression were detected using a high content screening (HCS) assay. The cell cycle and apoptosis of PC-3M cells were tested by flow cytometry. B16-F10-luc-G5 cardinoma cells were injected into the lateral tail vein of 6-week old male Balb/c nude mice and heparin 30 mg/kg was administered iv 30 min before and 24 h after injection. The metasis of B16-F10-luc-G5 cells was detected by bioluminescence assay. Activated partial thromboplastin time (APTT) and hemorheological parameters were measured on d 14 after injection of B16-F10-luc-G5 carcinoma cells in Balb/c mice. The global protein changes in PC-3M cells and frozen lung tissues from mice burdened with B16-F10-luc-G5 cells were determined by 2-dimensional gel electrophoresis and image analysis. The protein expression of vimentin and 14-3-3 zeta/delta was measured by Western blot. The mRNA transcription of vimentin, transforming growth factor (TGF)-β, E-cadherin, and α(v)-integrin was measured by RT-PCR. Heparin 25 and 125 μg/mL significantly inhibited the proliferation, arrested the cells in G(1) phase, and suppressed BrdU incorporation and Ki67 expression in PC-3M cells compared with the model group. But it had no significant effect on apoptosis of PC-3M cells. Heparin 30 mg/kg markedly inhibits the metastasis of B16-F10-luc-G5 cells on day 8. Additionally, heparin administration maintained relatively normal red blood hematocrit but had no influence on APTT in nude mice burdened with B16-F10-luc-G5 cells. Thirty of down-regulated protein spots were identified after heparin treatment, many of which are related to tumor development, extracellular signaling, energy metabolism, and cellular proliferation. Vimentin and 14-3-3 zeta/delta were identified in common in PC-3M cells and the lungs of mice bearing B16-F10-luc-G5 carcinoma cells. Heparin 25 and 125 μg/mL decreased the protein expression of vimentin and 14-3-3 zeta/delta and the mRNA expression of α(v)-integrin. Heparin 125 μg/mL decreased vimentin and E-cadherin mRNA transcription while increased TGF-β mRNA transcription in the PC-3M cells, but the differences were not significant. Transfection of vimentin-targeted siRNA for 48 h significantly decreased the BrdU incoporation and Ki67 expression in PC-3M cells. Heparin inhibited PC-3M cell proliferation in vitro and B16-F10-luc-G5 cells metastasis in nude mice by inhibition of vimentin, 14-3-3 zeta/delta, and α(v)-integrin expression.


Multivariate genome-wide covariance analyses of literacy, language and working memory skills reveal distinct etiologies.
Several abilities outside literacy proper are associated with reading and spelling, both phenotypically and genetically, though our knowledge of multivariate genomic covariance structures is incomplete. Here, we introduce structural models describing genetic and residual influences between traits to study multivariate links across measures of literacy, phonological awareness, oral language, and phonological working memory (PWM) in unrelated UK youth (8-13 years, N = 6453). We find that all phenotypes share a large proportion of underlying genetic variation, although especially oral language and PWM reveal substantial differences in their genetic variance composition with substantial trait-specific genetic influences. Multivariate genetic and residual trait covariance showed concordant patterns, except for marked differences between oral language and literacy/phonological awareness, where strong genetic links contrasted near-zero residual overlap. These findings suggest differences in etiological mechanisms, acting beyond a pleiotropic set of genetic variants, and implicate variation in trait modifiability even among phenotypes that have high genetic correlations.


[Phylogenetic analyses of some important Paris species based on sequences of matK gene].
The matK genes of 10 samples in Paris from Hunan, Yunnan and Jilin provinces were sequenced and compared. The phylogenetic tree was constructed based on the matK gene sequences and the ten pairs samples were divided into four groups. The results did not support the reality of four taxa named P. polyphylla var. pseudothibetica, P. polyphylla var. yunnanensis, P. polyphylla var. appendiculata and P. polyphylla var. chinenis. They are supposed to be treated as different forms of P. polyphylla var. polyphylla.


Blockade of GABA uptake with tiagabine inhibits audiogenic seizures and reduces neuronal firing in the inferior colliculus of the genetically epilepsy-prone rat.
Tiagabine is a new anticonvulsant drug that blocks the uptake of GABA, prolonging the action of this inhibitory transmitter. In the present study the effects of systemically administered tiagabine [30 mg/kg, ip (ED50)] were examined on audiogenic seizure (AGS) severity and neuronal firing in the inferior colliculus (IC) in the freely moving genetically epilepsy-prone rat (GEPR-9). The IC is known to be critical to AGS initiation. The effects of focal microinjection of tiagabine into the IC were also examined. Bilateral focal microinjection of tiagabine into the IC significantly reduced seizure severity in the GEPR-9. Systemically administered tiagabine also produced a significant reduction in seizure severity in the GEPR-9. Tiagabine produced a reduction in IC (central nucleus) neuronal firing, which was significant only at high acoustic intensities (90-105 dB), concomitant with the considerable reduction in seizure severity. These data are consistent with enhancement by tiagabine of gamma-aminobutyric acid (GABA)-mediated inhibition in IC, which is most prominent at high acoustic intensities. The time course of the reduction in neuronal firing of IC neurons paralleled the reduction in seizure severity. Previous studies have shown that two forms of GABA-mediated inhibition (intensity-induced and offset inhibition) in IC neurons are most prominent at high stimulus intensities, which are required to induce AGS. The blockade of GABA uptake by tiagabine may act to inhibit audiogenic seizures, in part, by intensifying these naturally occurring forms of acoustically evoked inhibition in inferior colliculus neurons.


Aromatase inhibitors and mood disturbances.
We describe the case of a 56-year old woman with no prior psychiatric history who was diagnosed with hormone receptor positive early-stage breast cancer and who developed severe mood changes after administration of anastrozole, which resolved after discontinuation of treatment. Aromatase inhibitors (AIs) are the preferred hormonal approach for postmenopausal women with estrogen hormone sensitive breast cancer. The third-generation agents (anastrozole, letrozole, and exemestane) have been shown to be more effective and safer than the selective estrogen receptor modulators tamoxifen and raloxifen. Treatment strategies with these agents include the use of an AI as an upfront strategy for 5 years, as a sequential approach after 2-3 years of tamoxifen, or as extended use after the classical 5 years of tamoxifen. The side effects of AIs, as compared with selective estrogen receptor modulators, are different, reflecting the specific mechanism of action of these drugs. AIs are well tolerated and cause a lower incidence of gynecological symptoms (vaginal bleeding, discharge, and endometrial neoplasia), venous thromboembolic events, and hot flashes compared with tamoxifen. However, the use of AIs have been associated with loss of bone density, arthralgia, myalgia, a negative effect on lipid metabolism, and cardiovascular risk (Tomao et al., 2011). Mood disturbances, somnolence, anxiety, fatigue, hot flashes, and memory impairment have been reported among patients receiving anastrozole as adjuvant therapy.


Evolving public health nursing roles: focus on community participatory health promotion and prevention.
Public health nursing (PHN) practice is population-focused and requires unique knowledge, competencies, and skills. Early public health nursing roles extended beyond sick care to encompass advocacy, community organizing, health education, and political and social reform. Likewise, contemporary public health nurses practice in collaboration with agencies and community members. The purpose of this article is to examine evolving PHN roles that address complex, multi-causal, community problems. A brief background and history of this role introduces an explanation of the community participation health promotion model. A community-based participatory research project, Youth Substance Use Prevention in a Rural County provides an exemplar for description of evolving PHN roles focused on community health promotion and prevention. Also included is discussion about specific competencies for PHNs in community participatory health promoting roles and the contemporary PHN role.


An accurate coarse-grained model for chitosan polysaccharides in aqueous solution.
Computational models can provide detailed information about molecular conformations and interactions in solution, which is currently inaccessible by other means in many cases. Here we describe an efficient and precise coarse-grained model for long polysaccharides in aqueous solution at different physico-chemical conditions such as pH and ionic strength. The Model is carefully constructed based on all-atom simulations of small saccharides and metadynamics sampling of the dihedral angles in the glycosidic links, which represent the most flexible degrees of freedom of the polysaccharides. The model is validated against experimental data for Chitosan molecules in solution with various degree of deacetylation, and is shown to closely reproduce the available experimental data. For long polymers, subtle differences of the free energy maps of the glycosidic links are found to significantly affect the measurable polymer properties. Therefore, for titratable monomers the free energy maps of the corresponding links are updated according to the current charge of the monomers. We then characterize the microscopic and mesoscopic structural properties of large chitosan polysaccharides in solution for a wide range of solvent pH and ionic strength, and investigate the effect of polymer length and degree and pattern of deacetylation on the polymer properties.


Comparative analysis of carbohydrate residues in the midgut of phlebotomines (Diptera: Psychodidae) from colony and field populations from Amazon, Brazil.
Leishmaniasis are worldwide diseases that occur in 98 countries including Brazil, transmitted by the bite of female phlebotomines during blood feeding. In Brazil it is known that some species of sand flies as Lutzomyia longipalpis sensun latum (vector of Leishmania infantum chagasi), Lutzomyia flaviscutellata (vector of Leishmania (Leishmania) amazonensis) and Lutzomyia antunesi [suspected vector of Leishmania (Viannia) lindenbergi] are incriminated of transmitting the parasite Leishmania for the vertebrate host. The phlebotomine-parasite is mediated by the attachment of the promastigote lipophosphoglycan (LPG) to the midgut epithelium. However, another mechanism that is LPG-independent and mediated by N-acetyl-galactosamine (GalNAc) seems to occur in some species of phlebotomines that are classified as permissive. The aim of this study was to characterize the carbohydrate residues that, probably, play a role in parasite attachment to the midgut of phlebotomine from colony and field populations from the Brazilian Amazonian region. We observed the presence of GalNAc, mannose, galactose and GlcNAc in all phlebotomine species. A binding assay between L. (L.) amazonensis and L. i.chagasi to the midguts of different species of phlebotomines was performed. The attachment of both Leishmania and vector species suggests the presence of GalNAc on the midgut surfaces. Thus, these results suggested that GalNAc is a possible binding sites of Leishmania in sand flies from the Brazilian Amazonian region.


Palliative urinary diversion in patients with advanced pelvic malignancy.
The survival patterns of 90 patients with advanced pelvic malignancy and bilateral ureteral obstruction treated with urinary diversion are reviewed. Cell type, presence or absence of prior treatment, or degree of renal decompensation had no specific correlation with length of survival. The youngest age group ranging from 27 to 49 years had a significantly shorter survival than the remainder of the patients. In patients who received prior treatment, an increasing time interval from original diagnosis of malignancy to diversion was associated with a longer median survival. Thirty patients lived six months or more after surgery and spent an average of 14% of their remaining life in the hospital. Guidelines for selection of patients who might benefit from urinary diversion are presented.


Midterm results with the use of polycarbonate urethane heterografts for dialysis access.
Dialysis access surgery is currently one of the most common vascular operations as the dialysis patient population increases. Although autogenous arteriovenous fistulae stand as the preferred method of access due to excellent patency and lower complication rates, grafts may provide alternative approaches when an autogenous fistula is impractical usually due to depleted veins. We aimed in this study to assess early and midterm outcome with the use of Expedial heterografts (LeMaitre Vascular Ltd., Wrexham, UK) for angioaccess between October 2000 and December 2004. Patients were prospectively followed for pre- and peri-operative course with 1st, 6th and 12th month outpatient controls for patency and complication rates. A total of 34 heterografts were implanted in 30 patients (22 males and 8 females; median age 60.6 years, range 32 - 70). The mean followup for 30 patients were 16.3 +/- 6.1 (range 4 - 30) months. 28 grafts (82.4%) were placed in forearm position. Primary and secondary patencies were found as 81% and 94%, respectively (p = 0.15), with the median censored primary and secondary patencies of 27 +/- 1.7 months (95% CI, 23.38 to 30.67) and 30.42 +/- 1.1 months (95% CI, 28.30 to 32.54), respectively. Only presence of diabetes was found as a significant risk factor in the regression model (p = 0.01). We suggest that the polycarbonate urethane heterografts with acceptable patency/complication rates and shorter maturation times for dialysis access serve an alternative for these patients.


Clinical and Laboratory Outcomes in HIV-1 and HTLV-1/2 Coinfection: A Systematic Review.
To perform a systematic review to describe the available findings on clinical outcomes in HIV-1 and HTLV-1/HTLV-2 co-infected individuals since 1995. This Systematic Review used PECO criteria follow by PRISMA reporting guidelines and registered as CRD42021279062 (Prospero database). The Newcastle-Ottawa Scale assessed the methodological quality of included studies. A systematical search in PubMed/MEDLINE, Embase, Web of Sciences databases for cross-sectional, case-control, or cohort studies design to identify clinical and laboratorial outcomes related to HIV-1 and HTLV-1/2 coinfection. Search strategy: [("HIV-1" AND "HTLV-1" OR "HTLV-2") AND ("Coinfection") AND (1990/01/01:2021/12/31[Date- Publication])]. A total of 15 articles were included on this systematic review describing data of 2,566 mono and coinfected patients, 58% male, with mean age was 35.7 ± 5.7 years. HIV-1 and HTLV-1 coinfected patients were more likely to had shorter survival and faster progression to death or mortality than monoinfected ones. Coinfected had higher CD4 cell counts and less likelihood of ART use. In addition, higher frequency of diseases like ichthyosis (22.2 vs. 6.8%), scabies (18.6 vs. 0%), candidiasis (42 vs. 12%), Strongyloidiasis (15.4 vs. 2%) and neurological manifestations like encephalopathy, peripheral neuropathy and HAM/TSP were more frequently reported in coinfected patients. HIV-1 and HTLV-1 coinfection and HIV-1 and HTLV-1 /2 triple coinfection were related to shorter survival, higher mortality rate, and faster progression to death, while coinfection by HIV-1/HTLV-2 seems to have neutral association with longer survival, slower AIDS progression, and lower mortality rate. The available evidence indicates an urgent need for prevention and control measures, including screening, diagnosis, and treatment of HIV-1 and HTLV-1/2 coinfected patients. Test-and-treat strategy for patients living with HIV in areas endemic for HTLV infection is mandatory, to avoid the risks of delayed therapy and death for coinfected patients. https://www.crd.york.ac.uk/prospero/, identifier: CRD42021279062.


A narrative evaluation of a psychoeducation and a therapeutic alliance intervention for parents of persons with a severe mental illness.
Most attempts to study the impact of psychosocial interventions on parents of persons with severe mental illness (SMI) are quantitative. The purpose of the present study was to investigate the subjective experience of parents of persons with SMI who participated in either a psychoeducational intervention which emphasized providing information on the illness and support, or a therapeutic alliance focused intervention (TAFI) which emphasized the alliance between the group members and group leaders. Ninety-three parents, who participated in either one of these two interventions, were interviewed using the Narrative Evaluation of Intervention Interview. Results show that participants found both interventions to be beneficial with no statistical differences in the level of perceived change. Themes describing change in relating to illness were significantly more frequently mentioned by participants in the TAFI group, whereas significantly more participants in the family psychoeducation interventions reported that implementation and information provided contributed to positive change. Also participants in the TAFI reported significantly more often that group regulation contributed to change. As both interventions were perceived as contributing, the findings support the relationship orientation to psychosocial interventions, which stresses the quality of the social support and interpersonal interaction as the source of positive outcomes of intervention.


Presence of Even a Small Ground-Glass Component in Lung Adenocarcinoma Predicts Better Survival.
While lepidic-predominant lung adenocarcinomas are known to have better outcomes than similarly sized solid tumors, the impact of smaller noninvasive foci within predominantly solid tumors is less clearly characterized. We tested the hypothesis that lung adenocarcinomas with even a small ground-glass opacity (GGO) component have a better prognosis than otherwise similar pure solid (PS) adenocarcinomas. The maximum total and solid-component diameters were determined by preoperative computed tomography in patients who underwent lobar or sublobar resection of clinical N0 adenocarcinomas without induction therapy between May 2003 and August 2013. Survival between patients with PS tumors (0% GGO) or tumors with a minor ground-glass (MGG) component (1%-25% GGO) was compared by Kaplan-Meier and Cox analyses. A total of 123 patients met the inclusion criteria, comprising 54 PS (44%) and 69 MGG (56%) whose mean ground-glass component was 18 ± 7%. The solid component tumor diameter was not significantly different between the groups (2.3 ± 1.2 cm vs. 2.5 ± 1.3 cm, P = .2). Upstaging to pN1-2 was more common for the PS group (13% [7/54] vs. 3% [2/69], P = .04), but the distribution of pathologic stage was not significantly different between the groups (PS 76% stage I [41/54] vs. MGG 80% stage I [55/69], P = .1). Having a MGG component was associated with markedly better survival in both univariate analysis (MGG 5-year overall survival 86.7% vs. PS 64.5%, P = .001) and multivariable survival analysis (hazard ratio, 0.30, P = .01). Patients with resected cN0 lung adenocarcinoma who have even a small GGO component have markedly better survival than patients with PS tumors, which may have implications for both treatment and surveillance strategies.


SCRAPPER Selectively Contributes to Spontaneous Release and Presynaptic Long-Term Potentiation in the Anterior Cingulate Cortex.
SCRAPPER is an E3 ubiquitin ligase expressed in presynaptic terminals, neural cell body, and dendrites of the hippocampus and cortex, which is coded by the FBXL20 gene. SCRAPPER is known to regulate synaptic transmissions and long-term potentiation (LTP) in the hippocampus, but no report is available for the cortex. Here we show genetic evidence for critical roles of SCRAPPER in excitatory transmission and presynaptic LTP (pre-LTP) of the anterior cingulate cortex (ACC), a critical cortical region for pain, anxiety, and fear. Miniature and spontaneous releases, but not evoked release, of glutamate were significantly increased in SCRAPPER knock-out (SCR-KO) mice. Interestingly, SCRAPPER selectively contributes to the increases of frequency and amplitude. The pre-LTP in the ACC was completely blocked in SCR-KO mice. Our results thus provide direct evidence for SCRAPPER in both spontaneous release and pre-LTP in the ACC and reveal a potential novel target for treating anxiety-related disease.SIGNIFICANCE STATEMENT The anterior cingulate cortex (ACC) plays critical roles in pain, anxiety, and fear. Peripheral injury induces long-term changes in synaptic transmission in the ACC. Our recent study found that a presynaptic form of LTP (pre-LTP) in the ACC contributes to chronic pain-induced anxiety. Here, we show that SCRAPPER plays a critical role in ACC pre-LTP as well as synaptic transmission.


Carcinoma meningitis secondary to non-small cell lung cancer: combined modality therapy.
Leptomeningeal metastases (LM) are increasingly diagnosed as anticancer therapies become more effective and result in prolonged patient survival. To evaluate survival, cause of death, and treatment-related toxic effects in patients undergoing combined modality therapy for LM of non-small cell lung cancer. Thirty-two patients (age range, 48-73 years; median, 57 years) with LM attributable to metastatic non-small cell lung cancer were treated prospectively. Neurologic presentation included headache (11 patients), cranial neuropathies (9), ataxia (5), cauda equina syndrome (3), myelopathy (3), meningismus (2), radiculopathy (2), and confusion (1). All patients underwent radiographic evaluation to determine the extent of central nervous system disease followed by radiotherapy (16 patients) and sequential and intraventricular chemotherapy (methotrexate in 32 patients; cytarabine in 16; and thiotepa in 6). Twelve patients received concurrent systemic chemotherapy. Central nervous system imaging demonstrated interrupted cerebrospinal fluid flow (13 patients), parenchymal brain metastases (9), subarachnoid nodules (8), hydrocephalus (5), and epidural spinal cord compression (2). Cytological responses were seen in 17 patients to first-line chemotherapy, 8 to second-line chemotherapy, and 2 to third-line chemotherapy. Treatment-related toxic effects included 20 patients with aseptic meningitis (grade 2 in 16; grade 3 in 4) and 12 patients with grade 3 or 5 thrombocytopenia or neutropenia (4 related to intraventricular chemotherapy). Median survival was 5 months (range, 1-12 months). Nineteen patients died of progressive LM or combined LM and systemic disease progression. Patients with persistent interruption of cerebrospinal fluid flow fared worse than patients with normal cerebrospinal fluid flow (median survival, 4 vs 6 months; P<.05). Leptomeningeal metastases in patients with non-small cell lung cancer may be palliated with combined modality therapy; however, therapy and survival is based on the extent of central nervous system disease present at pretreatment evaluation.


Pharmacokinetic Analysis of Peptide-Modified Nanoparticles with Engineered Physicochemical Properties in a Mouse Model of Traumatic Brain Injury.
Peptides are used to control the pharmacokinetic profiles of nanoparticles due to their ability to influence tissue accumulation and cellular interactions. However, beyond the study of specific peptides, there is a lack of understanding of how peptide physicochemical properties affect nanoparticle pharmacokinetics, particularly in the context of traumatic brain injury (TBI). We engineered nanoparticle surfaces with peptides that possess a range of physicochemical properties and evaluated their distribution after two routes of administration: direct injection into a healthy mouse brain and systemic delivery in a mouse model of TBI. In both administration routes, we found that peptide-modified nanoparticle pharmacokinetics were influenced by the charge characteristics of the peptide. When peptide-modified nanoparticles are delivered directly into the brain, nanoparticles modified with positively charged peptides displayed restricted distribution from the injection site compared to nanoparticles modified with neutral, zwitterionic, or negatively charged peptides. After intravenous administration in a TBI mouse model, positively charged peptide-modified nanoparticles accumulated more in off-target organs, including the heart, lung, and kidneys, than zwitterionic, neutral, or negatively charged peptide-modified nanoparticles. The increase in off-target organ accumulation of positively charged peptide-modified nanoparticles was concomitant with a relative decrease in accumulation in the injured brain compared to zwitterionic, neutral, or negatively charged peptide-modified nanoparticles. Understanding how nanoparticle pharmacokinetics are influenced by the physicochemical properties of peptides presented on the nanoparticle surface is relevant to the development of nanoparticle-based TBI therapeutics and broadly applicable to nanotherapeutic design, including synthetic nanoparticles and viruses.


Opioid receptor subtypes in the rat spinal cord: electrophysiological studies with mu- and delta-opioid receptor agonists in the control of nociception.
We have compared the ability of selective mu- and delta-opiate agonists to modulate nociceptive transmission at the level of the rat dorsal horn using electrophysiological approaches. Single-unit extracellular recordings were made from neurones in the lumbar dorsal horn of the intact rat under halothane anaesthesia. Neurones could be activated by both A- and C-fibre electrical stimulation (and by natural innocuous and noxious stimuli). Agonists were applied directly onto the cord in a volume of 50 microliters. The intrathecal administration of 3 agonists, Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO) (mu-selective) (2 X 10(-3)-10 nmol) Tyr-D-Thr-Gly-Phe-Leu-Thr (DTLET) (mu/delta) (7 X 10(-4)-70 nmol), and cyclic Tyr-D-Pen-Gly-Phe-D-Pen (DPDPE) (delta) (2 X 10(-2)-100 nmol) produced dose-dependent inhibitions of C-fibre-evoked neuronal activity whilst A-fibre activity was relatively unchanged. DAGO produced near-maximal inhibitions which could be completely reversed by naloxone (1.5 nmol) whilst DPDPE causes less marked inhibitions which could only be partially reversed by naloxone (1.5-13.5 nmol). DTLET produced effects intermediate to those of DAGO and DPDPE. The results suggest that both mu- and delta-opioid receptors can modulate the transmission of nociceptive information in the rat spinal cord.


Typical isolated ectrodactyly of hands and feet: early antenatal diagnosis.
Ectrodactyly is a rare dominant autosomal malformation with variable expression. Herein we report a case early diagnosed by ultrasound at 15 weeks of gestation of isolated ectrodactyly involving the four limbs. The sonographic findings were bilateral split hands and split foot. Diagnosis of typical isolated ectrodactyly was pathologically confirmed. Clinical forms, pathogenesis, differential diagnosis, and early prenatal diagnosis are discussed.


Signal transduction in the activation of spermatozoa compared to other signalling pathways: a biological networks study.
In this paper we represented Spermatozoa Activation (SA) the process that leads male gametes to reach their fertilising ability of sea urchin, Caenorhabditis elegans and human as biological networks, i.e. as networks of nodes (molecules) linked by edges (their interactions). Then, we compared them with networks representing ten pathways of relevant physio-pathological importance and with a computer-generated network. We have found that the number of nodes and edges composing each network is not related with the amount of published papers on each specific topic and that all the topological parameters examined are similar in all the networks, thus conferring them a scale free topology and small world behaviour. In conclusion, SA topology, independently from the reproductive biology of considered organism, as others signalling networks is characterised by robustness against random failure, controllability and efficiency in signal transmission.