Antiparasitic antioxidant phenylpropanoids and iridoid glycosides from Tecoma mollis.
A radical scavenging guided phytochemical study on the stem bark of Tecoma mollis afforded seven active phenylpropanoid glycosides (1-7), including a new one (4), and one iridoid (8). The structures of the isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Compounds (1-7) displayed promising antioxidant activity (DPPH assay) in relation to ascorbic acid (positive control). The antimicrobial activity for compounds (1-8) was evaluated against five bacterial and five fungal strains. The isolated compounds exhibited nonselective weak to moderate antimicrobial activity. The highest antileishmanial activity against Leishmania donovani was observed for compound (7) with an IC₅₀ value of 6.71 μg/ml, using pentamidine and amphotericin B as drug controls. Compound (5) exhibited moderate antimalarial activity (45% inhibition) against chloroquine sensitive (D6) clones of Plasmodium falciparum.


Preparation of a protein micro-array using a photo-reactive polymer for a cell-adhesion assay.
A protein micro-array, called a "cell chip" was constructed by using a photo-reactive polymer for a cell-adhesion assay. Various amounts of albumin or fibronectin were covalently immobilized on a polystyrene dish using a micro-spotter with a dip pen. First, poly(acrylic acid) carrying azidophenyl groups was synthesized as the photo-reactive polymer. Secondly, the aqueous solution of a photo-reactive polymer (several nanoliters) was cast using the dip pen of the micro-spotter and dried in air. Subsequently, aqueous solutions of proteins were cast on the same place using the micro-spotter. After drying, the dish was irradiated with ultraviolet light. Finally, the immobilization was confirmed by staining with a dye. The immobilization was stable even after washing with Tween-20. The protein-immobilized area depended on the manipulation of the micro-spotter and the size of the dip pen. Subsequently, cell adhesion on the photo-immobilized protein micro-array was investigated. The adhesion behavior of cells depended on the kind of immobilized proteins and the kind of cells. The protein micro-array will be useful for cell diagnosis and for the selection of biomaterials to regulate cell behavior.


Temperature excursions at the pulp-dentin junction during the curing of light-activated dental restorations.
Excessive heat produced during the curing of light-activated dental restorations may injure the dental pulp. The maximum temperature excursion at the pulp-dentin junction provides a means to assess the risk of thermal injury. In this investigation we develop and evaluate a model to simulate temperature increases during light-curing of dental restorations and use it to investigate the influence of several factors on the maximum temperature excursion along the pulp-dentin junction. Finite element method modeling, using COMSOL 3.3a, was employed to simulate temperature distributions in a 2D, axisymmetric model tooth. The necessary parameters were determined from a combination of literature reports and our measurements of enthalpy of polymerization, heat capacity, density, thermal conductivity and reflectance for several dental composites. Results of the model were validated using in vitro experiments. Comparisons with in vitro experiments indicate that the model provides a good approximation of the actual temperature increases. The intensity of the curing light, the curing time and the enthalpy of polymerization of the resin composite were the most important factors. The composite is a good insulator and the greatest risk occurs when using the light to cure the thin layer of bonding resin or in deep restorations that do not have a liner to act as a thermal barrier. The results show the importance of considering temperature increases when developing curing protocols. Furthermore, we suggest methods to minimize the temperature increase and hence the risk of thermal injury. The physical properties measured for several commercial composites may be useful in other studies.


Perineal hernia repair after abdominoperineal resection (APR) with the laparoscopic-peritoneal dual fixation technique.
Perineal hernia (PH) following abdominoperineal resection (APR) is a rare but challenging problem. Although different techniques have been described in literature, the recurrence rate is still remarkable, and there is no consensus regarding the optimal repair approach. In the present study, we reported our experience based on a consecutive series of ten cases. Ten symptomatic large perineal hernias were repaired exclusively with the same laparoscopic-perineal dual fixation technique. Key steps consist laparoscopic adhesiolysis, hernia contents reduction, open excess perineal hernia sac resection, and mesh placement and dual fixation. Frist, a coated mesh was fixed to the sacrum and pelvic sidewalls with the metallic tacks in the laparoscopic step, second, the mesh was fixed anteriorly to urogenital diaphragm and laterally to the sacrotuberous ligament with permanent sutures in the perineal step. Ten symptomatic PHs were repaired by the same laparoscopic-perineal dual fixation technique, 6 males and 4 females, median age at the time of repair was 69.5 years (range 66-77 years), the BMI was 24 ± 1. Four concomitant procedures were performed, including bilateral inguinal hernia repair with the transabdominal preperitoneal repair (TAPP) in one case, and laparoscopic parastomal hernia repair in two patients. The average operative time was 171 ± 45 min; the postoperative average hospital stay was 14 ± 4 days. There was no perineal hernia recurrence during the follow-up period (the median follow-up was 42 months; range 1-63 months). Perineal hernia after APR is a rare and challenging postoperative complication, although many different approaches have been described, the recurrence is still high and the best method cannot be drawn. The present laparoscopic-perineal dual fixation approach proved to be a reproducible, effective and durable technique, and gave excellent results during the medium-long-term follow-up.


Bone metastasis from malignant phyllodes breast tumor: report of two cases.
Phyllodes tumors are rare fibroepithelial tumors accounting for less than 1 % of all breast neoplasms. They are malignant in 20 % of cases. Only a few cases of malignant phyllodes tumors metastatic to bone have been reported. Case 1: A 40 year-old white woman presented with three-week history of pain and functional impairment of the left lower limb. Her clinical past was remarkable for previous left mastectomy and radiotherapy for malignant phyllodes tumor performed one year ago. Computed tomography revealed a moth-eaten appearance of the left femoral head. The patient underwent computed guided femoral head biopsy. Pathological findings were consistent with metastatic malignant phyllodes tumor. The patient received ifosfamide and adriamycin chemotherapy. She is doing well without any evidence of progression on her imaging follow- up after 8 months. Case 2: A 48 year-old white woman, with history of bilateral mastectomy and radiotherapy for malignant phyllodes tumor performed one and two year ago, presented with four-week left lower quadrant abdominal pain. Computed tomography and magnetic resonance imaging revealed a solid aggressive osteolytic mass of the left iliac bone with extensive soft tissue invasion. Biopsy of the tumor was performed and showed a sarcomatous proliferation consistent with metastatic malignant phyllodes tumor. The patient received the same chemotherapy regimen as in the first case but without any response on her imaging follow up after 6 months. Malignant phyllodes tumor is a rare and aggressive fibroepithelial neoplasm. An accurate diagnosis of metastases should be based on clinicopathological correlation allowing exclusion of differential diagnoses. The goal of successful managing this tumor is early detection and complete resection prior to dissemination.


Case report - atypical hemolytic uremic syndrome triggered by influenza B.
Influenza A infections have been described to cause secondary hemolytic uremic syndrome and to trigger atypical hemolytic uremic syndrome (aHUS) in individuals with an underlying genetic complement dysregulation. To date, influenza B has not been reported to trigger aHUS. A 6-month-old boy presented with hemolytic uremic syndrome triggered by influenza B infection. Initially the child recovered spontaneously. When he relapsed Eculizumab treatment was initiated, resulting in complete and sustained remission. A pathogenic mutation in membrane cofactor protein (MCP) was detected. Influenza B is a trigger for aHUS and might be underreported as such. Influenza vaccination may protect patients at risk.


Behavioral treatment of night bingeing and rumination in an adult case of bulimia nervosa.
A 24-year-old female, diagnosed as bulimia nervosa with night bingeing and rumination, was treated by individual and group behavior therapy. A changing criterion design progressively adjusted the criterion for reinforcement as the treatment obtained diminution of night bingeing. Night bingeing was finally eliminated, without evidence of recurrence at 3 month and 2 year follow-ups. Rumination was regarded as a collateral behavior and diminished in tandem with reduction of night bingeing. Other improvements in bulimia nervosa were observed over the course of treatment.


MRI diagnosis of occult ganglion compression of the posterior interosseous nerve and associated supinator muscle pathology.
Occult interosseous ganglions in the proximal forearm can result in pain and decreased supination. We will describe the magnetic resonance imaging (MRI) diagnosis of an interesting case of supinator atrophy secondary to compression of the posterior interosseous branch of the radial nerve. A brief review of this entity follows.


Clinical Evidence for Thermometric Parameters to Guide Hyperthermia Treatment.
Hyperthermia (HT) is a cancer treatment modality which targets malignant tissues by heating to 40-43 °C. In addition to its direct antitumor effects, HT potently sensitizes the tumor to radiotherapy (RT) and chemotherapy (CT), thereby enabling complete eradication of some tumor entities as shown in randomized clinical trials. Despite the proven efficacy of HT in combination with classic cancer treatments, there are limited international standards for the delivery of HT in the clinical setting. Consequently, there is a large variability in reported data on thermometric parameters, including the temperature obtained from multiple reference points, heating duration, thermal dose, time interval, and sequence between HT and other treatment modalities. Evidence from some clinical trials indicates that thermal dose, which correlates with heating time and temperature achieved, could be used as a predictive marker for treatment efficacy in future studies. Similarly, other thermometric parameters when chosen optimally are associated with increased antitumor efficacy. This review summarizes the existing clinical evidence for the prognostic and predictive role of the most important thermometric parameters to guide the combined treatment of RT and CT with HT. In conclusion, we call for the standardization of thermometric parameters and stress the importance for their validation in future prospective clinical studies.


Studies on the hydrolysis of bradykinin by angiotensin-converting enzyme (kininase II).
Arg-Pro-Pro-Gly-Phe, the N-terminal pentapeptide of bradykinin, is not an inhibitor of angiotensin-converting enzyme and is not hydrolyzed by the enzyme. Arg-Pro-Pro, the N-terminal tripeptide is a relatively potent (IC50 = 2.3 X 10(6) M) inhibitor but its higher homolog. Gly-Arg-Met-Lys-Arg-Pro-Pro is not an inhibitor of angiotensin-converting enzyme.


Combination Systemic Therapies in Advanced Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs): A Comprehensive Review of Clinical Trials and Prospective Studies.
There is an evolving landscape of systemic combination regimens for patients with advanced well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). In this review, we provide a comprehensive outline of the existing clinical trials/prospective studies investigating these combinations. PubMed was searched using key relevant terms to identify articles referring to GEP-NETs and combination treatments. No systematic search of the literature or metanalysis of the data was performed, and we focused on the most recent literature results. Primarily, phase 1 and 2 clinical trials were available, with a smaller number of phase 3 trials, reporting results from combination treatments across a wide range of antiproliferative agents. We identified significant variability in the anti-tumor activity of the reported combinations, with occasional promising results, but only a very small number of practice-changing phase 3 clinical trials. Overall, the peptide receptor radionuclide therapy (PRRT)-based combinations (with chemotherapy, dual PPRT, and targeted agents) and anti-vascular endothelial growth factor (VEGF) agent combinations with standard chemotherapy were found to have favorable results and may be worth investigating in future, larger-scale trials. In contrast, the immune-checkpoint inhibitor-based combinations were found to have limited applicability in advanced, well-differentiated GEP-NETs.


Diagnosis of acute Q fever with emphasis on enzyme-linked immunosorbent assay and nested polymerase chain reaction regarding the time of serum collection.
A commercially available enzyme-linked immunosorbent assay (ELISA) (Virion/Serion [Wuerzburg, Germany]), an indirect fluorescent antibody test (IFAT) (BIOS/Focus [Cypress, CA]), and a nested polymerase chain reaction (PCR) were explored for diagnosis of acute Q fever in reference to time of serum collection. Serum samples of 22 patients with acute Q fever collected around the fifth day of illness were included. A sensitivity of 30% by ELISA and 80% by IFAT (P = 0.1) was found for the first 5 days of illness and 92% by ELISA and 83% by IFAT during the sixth and eleventh day. PCR revealed a positive result in 8 cases (36%) with 6 cases deriving from the first 5 days of illness. We conclude that ELISA aids especially in the diagnosis of Q fever after 5 days of illness. The benefit of PCR as an additional tool to ELISA was especially evident in the early days of serum sampling.


Long duration of immunotherapy before radiosurgery might improve intracranial control of melanoma brain metastases.
Despite significant advances that have been made in management of metastatic melanoma with immune checkpoint therapy, optimal timing of combination immune checkpoint therapy and stereotactic radiosurgery is unknown. We have reported toxicity and efficiency outcomes of patients treated with concurrent immune checkpoint therapy and stereotactic radiosurgery. From January 2014 to December 2016, we analyzed 62 consecutive patients presenting 296 melanoma brain metastases, treated with gamma-knife and receiving concurrent immune checkpoint therapy with anti-CTLA4 or anti-PD1 within the 12 weeks of SRS procedure. Median follow-up time was 18 months (mo) (13-22). Minimal median dose delivered was 18 gray (Gy), with a median volume per lesion of 0.219 cm3. The 1-year control rate per irradiated lesion was 89% (CI 95%: 80.41-98.97). Twenty-seven patients (43.5%) developed distant brain metastases after a median time of 7.6 months (CI 95% 1.8-13.3) after gamma-knife. In multivariate analysis, positive predictive factors for intracranial tumor control were: delay since the initiation of immunotherapy exceeding 2 months before gamma-knife procedure (P=0.003) and use of anti-PD1 (P=0.006). Median overall survival (OS) was 14 months (CI 95%: 11-NR). Total irradiated tumor volume<2.1 cm3 was a positive predictive factor for overall survival (P=0.003). Ten patients (16.13%) had adverse events following irradiation, with four grade≥3. Predictive factors of all grade toxicity were: female gender (P=0.001) and previous treatment with MAPK (P=0.05). A long duration of immune checkpoint therapy before stereotactic radiosurgery might improve intracranial tumor control, but this relationship and its ideal timing need to be assessed in prospective trials.


The clinical management of acetaminophen poisoning in a community hospital system: factors associated with hospital length of stay.
Acetaminophen (APAP) overdose is the most common pharmaceutical poisoning. The objective of this study was to examine the management of patients admitted for treatment of APAP overdose. Factors impacting hospital length of stay (LOS) were of particular interest. This was a retrospective cohort study of patients admitted to Kaiser Permanente Northern California hospitals for APAP overdose from July 2003 through December 2007. Medical records were abstracted for patient demographic data, key factors of overdose, California Poison Control System (CPCS) contact, data regarding hospital course, transfer for liver transplantation, and death. Four hundred thirty-five patients were included. The mean hospital LOS was 66.5 h (95% CI 62.1, 71.0). Four patients (0.9%) died. Eight patients (1.8%) were transferred for liver transplantation, but all of these patients later recovered without transplant. Of 289 cases eligible for placement on the Rumack-Matthew nomogram (acute ingestion with known time of ingestion <24 h and normal liver enzymes), 161 (55.7%) had APAP levels above the "200" line and 77 (26.6%) fell below the "150" line. CPCS was contacted in 295 cases (67.8%). Mean LOS in cases with CPCS consultation was 61.9 h (95% CI 57.2, 66.5 h) versus 76.3 h (95% CI 66.6, 86.0 h) in those without. LOS in cases treated with IV NAC was 67.1 h (95% CI 57.7, 76.5 h) versus 66.4 h (95% CI 61.2, 71.5 h) in cases treated with oral NAC. Many patients admitted for APAP overdose had serum APAP levels below the minimum toxicity level. Use of IV NAC did not impact hospital LOS. CPCS consultation appeared to decrease mean hospital LOS.


Isolation and maintenance of Balantidium coli (Malmsteim, 1857) cultured from fecal samples of pigs and non-human primates.
Balantidium coli is a protozoa that can determine dysentery in humans, pigs and non-human primates having zoonotic potential. The lack of standardization in isolation and maintenance hinders the development of research on its biology and epidemiology. This study is aimed to standardize the isolation and maintenance of this parasite from animal feces, in culture medium, Pavlova modified. From 2012 to 2014, 1905 fecal samples were collected from captive animals of Rio de Janeiro. Were selected for isolation samples with a minimum of 10 trophozoites and/or 30 cysts of B. coli, totaling 88 pigs, 26 Cynomolgus and 90 rhesus macaques. In the presence of cysts, the sample was homogenized in saline solution, 500 μL was removed and inoculated into culture medium. The material that contained trophozoites the inoculum was made from 240 μL of fecal solution. All inoculate tubes with the subcultures were kept at 36°C, and sterile rice starch was always added to the medium. The parasites isolate from pigs, 34%, and from Cynomolgus 38.4% were maintained in vitro for a period of more than 24 months. These procedures proved to be adequate for isolation and maintenance of B. coli from different animals, they were found to be inexpensive and easy to perform.


Secreted sphingomyelins modulate low mammary cancer incidence observed in certain mammals.
Determining mechanisms that naturally protect species from developing cancer is critical in order to prevent and treat cancer. Here, we describe a novel cancer-suppressing mechanism, via the secretion of bioactive factors by mammary cells, that is present in domesticated mammals with a low mammary cancer incidence. Specifically, these bioactive factors induced triple-negative breast cancer cell (TNBC) death in vitro and reduced tumorigenicity in a xenograft TNBC mouse model in vivo. RNA deep sequencing showed significant downregulation of genes associated with breast cancer progression in secretome-cultured TNBC cells. Further in-depth multi-omics analysis identified sphingomyelins as key secreted factors, and their role was confirmed via inhibition of the sphingomyelin signaling pathway. We speculate that secreted sphingomyelins in the mammary gland of mammals with a naturally low incidence of mammary cancer mediate the elimination of cancer cells. This study contributes to the growing list of protective mechanisms identified in cancer-proof species.


Characterisation of an ELISA detecting immunoglobulin G to Mycobacterium avium subsp. paratuberculosis in bovine colostrum.
Although colostrum has been used to detect specific immunoglobulin (Ig) G to Mycobacterium avium subsp. paratuberculosis (MAP) in cattle, confounding, non-specific reactions can be a problem. The objectives of this study were to determine the proportion of non-specific ELISA reactions in samples of colostrum taken between 0 and 4 days-in-milk (DIM), and to assess the probability of an animal testing positive for MAP specific IgG over this time-period. Non-specific reactions were found in 3/365 (0.8%) of samples. The odds of an animal testing positive on day of calving were 130 times higher than at 4 DIM. The findings suggest colostral samples may have enhanced diagnostic potential over milk samples in determining if cattle have been exposed to or infected with MAP.


Co-treatment with probucol does not improve lung pathology in hydroxypropyl-β-cyclodextrin-treated Npc1-/- mice.
We previously reported the altered pulmonary function and pathology found in the mouse model of infantile Niemann-Pick C1 disease, the Npc1-/- mouse. Despite its salutary properties on brain and liver parameters, we did not find efficacious effects of hydroxypropyl-β-cyclodextrin (HPBCD) on pulmonary pathology. Since we had previously shown the beneficial effects of probucol on the somatic phenotype in the Npc1-/- mice, we have now studied the effects of combined therapy with HPBCD and probucol on the lung with mostly negative results. Body weight and lung weight for body weight were increased in parallel while inspiratory capacity for body weight was markedly decreased. Other physical, biochemical, and pulmonary function parameters were not much changed. There were trends towards improved lung elastance (p = 0.09) and compliance (p = 0.07).


Unusual presentation of obstructive sleep apnoea syndrome due to a giant mandible osteoma: case report and literature review.
Osteomas are benign lesions composed of mature compact and/or cancellous bone that grow continuously. Their pathogenesis is unknown. It has been considered to be a neoplasm, a developmental or reactive osteogenic lesion resulting from muscle traction on the periosteum, or due to trauma. Herein, we report an unusual case of giant osteoma of the mandible depressing the lateral pharyngeal wall, interfering with normal respiration during the night. The uniqueness of this case is related to snoring and sleep apnoea symptoms. In fact, he presented to our Department because daytime sleepiness hindered his work, and not for the evident facial swelling. We reported our experience in diagnosis, treatment and follow-up of this uncommon disease. Polysomnography, CT scan and 3-D PAS volume analysis are useful tools to study in detail the aetiology of apnoea and assess outcomes.


Transmural variation in autoregulation of right ventricular blood flow.
We examined transmurally the right coronary autoregulatory flow response to varied perfusion pressures in 11 anesthetized, open-chest dogs. Right coronary artery flow was measured electromagnetically, and its transmural distribution was defined with 15-micron radioactive microspheres. Heart rate, mean aortic blood pressure, right ventricular systolic pressure, end-diastolic pressure, and dP/dtmax were constant. At 100 mm Hg, subepicardial flow averaged 0.48 +/- 0.04 ml/min/g, and subendocardial flow averaged 0.56 +/- 0.05 ml/min/g. In contrast to the left coronary circulation, right coronary hypotension did not cause preferential subendocardial ischemia. As right coronary perfusion pressure was decreased from 100 to 40 mm Hg in five dogs, subepicardial and subendocardial flows were reduced similarly by 35-36%. As right coronary perfusion pressure was elevated from 100 to 150 mm Hg in six dogs, right ventricular subepicardial blood flow increased by 31%, whereas subendocardial blood flow increased by 70%. Right ventricular subendocardial-to-subepicardial flow ratios averaged 1.15-1.20 for perfusion pressures of 40 to 120 mm Hg, and they increased to 1.36 +/- 0.05 at 150 mm Hg. Right coronary artery autoregulatory closed-loop gain averaged 0.47 +/- 0.06 between 70 and 100 mm Hg and was greater than zero from 40 to 120 mm Hg. Between 120 and 150 mm Hg, gain fell to -0.15 +/- 0.10. Regional gain varied from 0.59 +/- 0.10 to 0.44 +/- 0.08 in subepicardium as pressure was decreased from 100 to 40 mm Hg. Subendocardial gains were similar to subepicardial gains over this pressure range.(ABSTRACT TRUNCATED AT 250 WORDS)


Efficacy and tolerability of ophthalmic epinastine assessed using the conjunctival antigen challenge model in patients with a history of allergic conjunctivitis.
Epinastine hydrochloride is a nonsedating antihistamine with a high affinity for histamine H(1) receptors, together with mast cell-stabilizing and anti-inflammatory activities. The aim of this study was to assess the efficacy and tolerability of topically administered ophthalmic epinastine using the conjunctival antigen challenge (CAC) model in patients with a history of allergic conjunctivitis. This prospective, single-center, randomized, double-masked, vehicle-controlled, Phase III clinical trial was conducted at the Ophthalmic Research Associates study center (North Andover, Massachusetts) from November 2000 to January 2001. Eligible participants were asymptomatic but had a history of allergic conjunctivitis and had positive CAC reactions at the initial screening (week 0) and at a confirmation visit (week 1). Patients were randomly assigned by eye to receive epinastine hydrochloride 0.05% ophthalmic solution in 1 eye and vehicle in the contralateral eye. Each eye received 1 drop of study medication 15 minutes before antigen application (onset challenge; week 3) or 8 hours before antigen application (duration challenge; week 5). Primary end points were ocular itching and conjunctival hyperemia. Itching was recorded 3, 5, and 10 minutes after antigen challenge. Hyperemia was recorded 5, 10, and 20 minutes after antigen challenge, as were secondary end points, which included eyelid swelling, episcleral and ciliary hyperemia, chemosis, tearing, and ocular mucous discharge. Tolerability was assessed by patient interview and slit-lamp biomicroscopy. Sixty-seven patients (37 females, 30 males; mean [SD] age, 38.4 [14.2] years [range, 12-67 years]) were included in the study. Mean severity scores for the following signs and symptoms were significantly lower with epinastine compared with vehicle at all time points after onset and duration challenges: ocular itching (P<0.001); eyelid swelling (P<0.001); conjunctival ( P<0.001), episcleral ( P<0.001), and ciliary hyperemia (P<0.001); and chemosis (P<or=0.009). The percentage of eyes with tearing was significantly lower with epinastine compared with vehicle at all time points (P<or=0.021), except at 5 minutes after the duration challenge. Adverse events (AEs), reported for 7.5% (5/67) of patients, included only symptoms of upper respiratory tract infection. No ocular or treatment-related AEs were reported. In this CAC model, multiple signs and symptoms of allergic conjunctivitis were significantly reduced by instillation of epinastine compared with vehicle. Epinastine showed prompt onset (3 minutes) and long duration of action (>or=8 hours). The tolerability of epinastine was similar to that of vehicle.


Premenstrual syndrome (PMS): a peri-menopausal perspective.
PMS (premenstrual syndrome) affects 30-40% of the reproductive female population and hence creates significant impairment amongst women of working age [1]. Having such an economical and financial impact makes it an important disorder to know more about in terms of diagnosis and treatment. In this article, as well as addressing diagnosis and treatments, we focus mainly on peri-menopausal women who are equally (if not more) affected by this disorder and who are subjected to PMS via a host of widely used hormonal treatments. We describe the vicious cycle that exists between exogenous progestogen stimulating PMS-like symptoms and the progestogen that is required for endometrial protection and ways of avoiding this. The treatment should address all concerns of the individual, namely contraceptive requirements, control of PMS and menopausal symptoms. The main theory behind treatment of PMS is to suppress ovulation along the hypothalamo-pituitary-ovarian axis, however neurotransmitters are also implicated in reducing sensitivity to progesterone via receptors, and therefore selective serotonin reuptake inhibitors are also useful. Surgical methods are strongly discouraged and are a last resort. With so many pitfalls, this article aims to tackle the issues commonly encountered with diagnosis and treatment of PMS in the peri-menopause.


Bronchial artery aneurysm disguised as a leiomyoma of the esophagus.
Bronchial artery aneurysm (BAA) is a rare entity with potentially fatal hemorrhagic complications. It is usually diagnosed using a computed tomography scan or angiography in emergency situations (clinical picture of aortic dissection or massive hemoptysis). We report a case of bronchial artery aneurysm where dysphagia was the predominant symptom. Thoracic computed tomography and endoscopic ultrasound seemed to indicate leiomyoma of the esophagus. The final diagnosis revealed a bronchial artery aneurysm.


Latent classes of maladaptive personality traits exhibit differences in social processing.
Social processing (SP) deficits manifest across numerous mental disorders. However, this research has been plagued by heterogeneity and a piecemeal approach whereby skills are examined in isolation rather than as part of an integrated cognitive system. Here, we combined two dimensional frameworks of psychopathology to address these limitations. We utilized the Alternative Model for Personality Disorders (AMPD) to distill trait-related heterogeneity within a community sample (n = 200), and the Research Domain Criteria (RDoC) 'Systems for Social Processes' to comprehensively assess SP. We first applied latent class analyses (LCA) to derive AMPD-based groups and subsequently contrasted the performance of these groups on a SP test battery that we developed to align with the RDoC SP constructs. Our LCA yielded four distinct subgroups. The recognizable trait profiles and psychopathological symptoms of these classes suggested they were clinically meaningful. The subgroups differed in their SP profiles: one displayed deficits regarding the self, a second displayed deficits in understanding others, a third displayed more severe deficits including affiliation problems, whilst the fourth showed normal performance. Our results support the link between clusters of maladaptive personality traits and distinctive profiles of SP deficits, which may inform research on disorders involving SP dysfunctions.


The effect of rheopheresis treatment on the cytokine profile in diabetic foot syndrome with hyperviscosity in the aspect of clinical changes: A preliminary study.
Rheopheresis is a selective extracorporal double cascade filtration treatment, which can extract high molecular weight proteins being responsible for hyperviscosity. As the whole blood and plasma viscosity decrease microcirculation improves. In this preliminary study we aimed to analyze additional beneficial effects of rheopheresis treatment with changes of pro-inflammantory cytokine levels in diabetic foot syndrome patients. Two rheopheresis treatments were performed for 6 patients with diabetic foot ulcer and/or neuropathy on consecutive days. Before and after the treatments whole blood and plasma viscosity, as well as IL-6, IL-8, and TNF-alpha serum levels were determined, and complex angiological and ENG examinations were performed. Rheopheresis decreased the whole blood and plasma viscosity, and the serum levels of IL-6, IL-8, and TNF-alpha were markedly reduced. The life quality of the patients improved, the ulcers healed, the pain decreased. Daily dose of analgesics decreased in the follow-up period (6 months). The ENG showed improving amplitude and/or normalizing conduction speed. Application of rheopheresis in patients with diabetic foot syndrome has a beneficial effect, providing favorable rheological condition, normalizing cytokine profile and reducing the sensorineural symptoms.


The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes. III. B-cell dependence for T-cell proliferation.
The nature of the helper lymphocytes in lymphocytosis-promoting factor (LPF)-induced proliferation was explored. Removal of macrophages from adherent splenocytes by either carbonyl-iron incubation or passage through Sephadex G-10 columns did not affect their synergistic function. Nor did cytolysis with Thy-1.2 antiserum and complement. The helper cells were found to be surface immunoglobulin-positive (sIg+) because they are retained by anti-Ig columns, susceptible to lysis by rabbit anti-mouse immunoglobulin and complement, and occurred in the sIg+ fractions of splenocytes after separation on the fluorescence-activated cell sorter. Further delineation of the surface markers on helper cells showed that complement receptors are not the determining marker for synergistic function. The requirement for B-helper cells in the stimulation of T lymphocytes by LPF is unique for a mouse of T-cell mitogen.


[Effect of chronic inflammation-induced basement membrane changes on esophageal carcinogenesis].
Basement membrane (BM) could regulate differentiation, proliferation, and polarity of esophageal epithelium, and its integrity is important for carcinogenesis. This study was to explore the effect of the BM changes induced by chronic inflammation on esophageal carcinogenesis and its possible mechanisms through investigating the relationship of BM changes and epithelial proliferation. The morphologic changes of BM in 10 specimens of invasive esophageal carcinoma tissue and 200 specimens of carcinoma adjacent tissue were observed with periodic acide-chiff staining (PAS); the correlations of inflammation score and histological type of esophageal epithelia to BM changes were analyzed. Of preceding specimens, the expression of laminin (LN), proliferating cell nuclear antigen (PCNA), and Ki-67 in 51 cases with typical BM changes were detected by immunohistochemistry; the correlation of LN to epithelial proliferation was analyzed. Dotted loss, piece loss, zone loss, and fragment thickening were observed at BM of hyperplasia, dysplasia, in situ carcinoma, and invasive carcinoma of esophageal epithelia. BM changes were related with inflammation score in epithelia (rs=0.795, P<0.05). PCNA and Ki-67 were expressed highly in the epithelia with changed BM (P<0.01). BM changes induced by chronic inflammation are correlated with aberrant proliferation of esophageal epithelia.


The Effect of Surgical Treatments for Trapeziometacarpal Osteoarthritis on Wrist Biomechanics: A Cadaver Study.
Studies have shown the effects of surgical treatments for trapeziometacarpal osteoarthritis on thumb biomechanics; however, the biomechanical effects on the wrist have not been reported. This study aimed to quantify alterations in wrist muscle forces following trapeziectomy with or without ligament reconstruction and replacement. A validated physiological wrist simulator replicated cyclic wrist motions in cadaveric specimens by applying tensile loads to 6 muscles. Muscle forces required to move the intact wrist were compared with those required after performing trapeziectomy, suture suspension arthroplasty, prosthetic replacement, and ligament reconstruction with tendon interposition (LRTI). Trapeziectomy required higher abductor pollicis longus forces in flexion and higher flexor carpi radialis forces coupled with lower extensor carpi ulnaris forces in radial deviation. Of the 3 surgical reconstructions tested post-trapeziectomy, wrist muscle forces following LRTI were closest to those observed in the intact case throughout the range of all simulated motions. This study shows that wrist biomechanics were significantly altered following trapeziectomy, and of the reconstructions tested, LRTI most closely resembled the intact biomechanics in this cadaveric model. Trapeziectomy, as a standalone procedure in the treatment of trapeziometacarpal osteoarthritis, may result in the formation of a potentially unfilled trapezial gap, leading to higher wrist muscle forces. This biomechanical alteration could be associated with clinically important outcomes, such as pain and/or joint instability.


Prevention of hip fractures.
For a 50-year old Caucasian woman today, the risk of a hip fracture over her remaining life-time is about 17%. Tomorrow the situation will clearly be worse because the continuous increase in life expectancy will cause a three-fold increase in worldwide fracture incidence over the next 60 years. Through diagnostic bone mass measurements at the hip and assessment of biochemical parameters, a great deal has been learned in recent years about reduction of hip fracture risk. Preventive strategies are based on prevention of falls, use of hip protectors, and prevention of bone fragility. The latter includes the optimization of peak bone mass during childhood, postmenopausal estrogen replacement therapy, and also late prevention consisting in reversing senile secondary hyperparathyroidism, which plays an important role in the decrease of skeletal strength. This secondary hyperparathyroidism, which results from both vitamin D insufficiency and low calcium intake, is preventable with vitamin D3 and calcium supplements. They have recently been shown capable of providing effective prevention of hip fractures in elderly women living in nursing homes, with a reduction of about 25% in the number of hip fractures noted in a 3-year controlled study in 3,270 women (intention-to-treat analysis). In conclusion, it is never too early to reduce the risk of osteoporosis and never too late to prevent hip fractures.


United States Pharmacopeia review of the black cohosh case reports of hepatotoxicity.
Black cohosh [Actaea racemosa L., formerly Cimicifuga racemosa (L.) Nutt.] is a botanical used mainly for the management of menopausal symptoms. Recently, regulatory agencies in Australia, Canada, and the European Union have released statements regarding the "potential association" between black cohosh and hepatotoxicity. In response, the Dietary Supplement Information Expert Committee of the US Pharmacopeia's Council of Experts reviewed safety information for black cohosh products. The Expert Committee analyzed information from human clinical case reports, adverse event reports, animal pharmacological and toxicological data, historical use, regulatory status, and contemporaneous extent of use. Reports were obtained from diverse sources, including the European Medicines Agency, Health Canada, the Australian Therapeutic Goods Administration, and the US Food and Drug Administration. Case reports pertaining to liver damage were evaluated according to the Naranjo causality algorithm scale. Thirty nonduplicate reports on use of black cohosh products concerning liver damage were analyzed. All the reports of liver damage were assigned possible causality, and none were probable or certain causality. The clinical pharmacokinetic and animal toxicological information did not reveal unfavorable information about black cohosh. Based on this safety review, the Dietary Supplement Information Expert Committee determined that black cohosh products should be labeled to include a cautionary statement. This is a change from the Expert Committee's decision of 2002, which required no such statement. With this decision, the US Pharmacopeia's Botanical Expert Committee may develop monographs for black cohosh, and the US Pharmacopeia may offer its verification programs to dietary supplement ingredient and product manufacturers.


Structural biology of glycoprotein hormones and their receptors.
Glycoprotein hormones regulate reproduction in vertebrates and exert their actions through specific G protein-coupled receptors on target cell surfaces. Structural information is now available for human chorionic gonadotropin (CG), follicle-stimulating hormone (FSH), and FSH bound to the extracellular binding domain of its receptor (FSHR(HB)). The recently determined structure of a human FSH-FSHR(HB) complex provides an explanation for the specificity of glycoprotein hormones binding to their receptors, and it suggests hypotheses concerning the mechanism of transmembrane signal transduction.


Heartwater serology: some problems with the interpretation of results.
Antibodies in the sera of domestic ruminants that have been infected with Ehrlichia bovis and other ehrlichial agents cross-react with the Kümm strain of Cowdria ruminantium used in the indirect fluorescent antibody test as antigen. These cross-reactions are also shown by the Elisa test in which the Ball 3 strain of the heartwater agent is used as antigen.


Inhibition of spontaneous AKR leukemia by multiple inoculations of Corynebacterium parvum.
In previous studies we have shown that AKR mice could be protected from spontaneous leukemia by specific immunotherapy in combination with splenectomy. In this experiment we investigated the effects of nonspecific immunotherapy with C. parvum in a similar regimen. It was found that bi-weekly, ip inoculations of 0.7 mg of C. parvum could significantly protect AKR mice from spontaneous tumors, and that splenectomy could not modify this effect. Thus, the spleen does not appear to play a determinant role in mediating the protective effects of C. parvum, as had been suggested in other systems.


Genetic structure and differentiation analysis of a Eurasian Uyghur population by use of 27 continental ancestry-informative SNPs.
Previously, we developed and validated a multiplex assay of 27 ancestry-informative markers (AIMs) for analyzing African (AFR), European (EUR), and East Asian (EAS) ancestry components. In this study, we typed and collectively analyzed a large Uyghur sample of 979 individuals to estimate the genetic coefficients of the 27 AIMs and investigate differentiation parameters between Uyghur and Han. The Uyghur allele frequencies ranged from 0.243 to 0.952, and heterozygosities ranged from 0.091 to 0.500. Values of F st 3 and I n 3 for EUR, Uyghur, and EAS ranged from 0.028 to 0.550 and 0.0002 to 0.345, respectively. The Uyghur population displays a substantial ancestry contribution of 50.3:49.7 (EUR:EAS) and was efficiently discriminated from Han Chinese with an accuracy of 99.285 %. All populations were clustered into AFR, EUR, EAS, and admixture groups of these three ancestries. Central Asian was obviously stratified from the other admixture populations of South Asians, North Asians, and the Americans. The 27 SNPs yield a circle with an average distance of 0.936 from the center (0, 0) in PCA analysis. Using this set, Chinese Uyghur and Han populations achieved accurate differentiation, and our updated genotype database (by citing 1000 Genomes data) of 43 worldwide populations is a useful resource for forensic applications and disease association studies.


Downregulation of PDCD4 through STAT3/ATF6/autophagy mediates MIF-induced PASMCs proliferation/migration and vascular remodeling.
To address the molecular mechanisms underlying macrophage migration inhibitory factor (MIF) induced pulmonary artery smooth muscle cells (PASMCs) proliferation, migration and vascular remodeling in pulmonary hypertension (PH), primary cultured rat PASMCs and monocrotaline (MCT)-induced rats with PH were applied in the present study. The results showed that MIF increased signal transducer and activator of transcription 3 (STAT3) phosphorylation, and then stimulated activating transcription factor 6 (ATF6) activation, subsequently triggered autophagy activation, which further led to programmed cell death factor 4 (PDCD4) lysosomal degradation, and eventually promoted PASMCs proliferation/migration. In lung tissues of MCT rats, MIF protein expression was elevated, phosphorylation of STAT3 and activation of ATF6 were increased, activation of autophagy was evident, and reduction of PDCD4 was observed. Intervention with MIF inhibitor 4-Iodo-6-phenylpyrimidine (4-IPP), ATF6 blocker melatonin or autophagy inhibitor chloroquine, confirmed the in vitro interaction among MIF, STAT3, ATF6, autophagy and PDCD4 in MCT induced rats with PH. Targeting MIF/STAT3/ATF6/autophagy/PDCD4 axis effectively prevented the development of PH by suppressing PASMCs proliferation and vascular remodeling. In conclusions, we demonstrate that MIF activates the STAT3/ATF6/autophagy cascade and then degrades PDCD4 leading to PASMCs proliferation/migration and pulmonary vascular remodeling, suggesting that intervention this axis might have potential value in management of PH.


Oculomotor abnormalities in a patient with fragile X-associated tremor/ataxia syndrome.
We present a case report of an 80-year-old man with Fragile X-associated tremor/ataxia syndrome (FXTAS) and acquired diplopia, strabismus, and other oculomotor abnormalities. This is the first case report of ocular abnormalities in a patient with FXTAS.


Expression of endogenous xenotropic retrovirus by methylcholanthrene-induced squamous cell carcinoma of the mouse respiratory tract.
As a model for human lung cancer, squamous cell carcinomas were induced by 3-methylcholanthrene in mouse tracheas which had been explanted to a subcutaneous site. The tumors that developed were examined for both ecotropic and xenotropic infectious murine leukemia virus (MuLV). From all squamous carcinomas--six out of six--a xenotropic MuLV was isolated. From some of the fibrosarcomas that occurred incidentally in our induction system, ecotropic MuLV was isolated. However, in the fibrosarcomas, no xenotropic MuLV at all was found.


Cardiac tamponade and pericardial effusion: respiratory variation in transvalvular flow velocities studied by Doppler echocardiography.
Cardiac tamponade has been associated with an abnormally increased respiratory variation in transvalvular blood flow velocities. To determine whether this finding is consistently present in cardiac tamponade, seven patients were studied prospectively with Doppler echocardiography before and after pericardiocentesis and the results were compared with those found in 20 normal adults and 14 asymptomatic patients with pericardial effusion who did not have definite clinical evidence of tamponade. Doppler ultrasound evaluation included measurement of mitral, tricuspid, aortic, pulmonary and central venous flow velocities, as well as left ventricular ejection and isovolumic relaxation times during inspiration, expiration and apnea. In the patients with severe cardiac tamponade, respiratory variation in transvalvular flow velocities and left ventricular ejection and isovolumic relaxation times were markedly increased compared with values in normal subjects and those obtained after pericardiocentesis. In the 14 asymptomatic patients with pericardial effusion but without overt tamponade, 7 showed respiratory variation in flow velocity similar to that of normal subjects. The other seven patients demonstrated increased respiratory change compared with normal, but less than that in the patients with tamponade. Clinical and hemodynamic data in this latter group suggest that these patients may represent an intermediate stage of pericardial effusion with an element of hemodynamic compromise.


Royal jelly can diminish secondary neuronal damage after experimental spinal cord injury in rabbits.
The aim of this experimental study was to investigate the neuroprotective effect of Royal jelly (RJ) on traumatic spinal cord injury (SCI). Twenty-one New Zealand male rabbits, weighing between 2.5 and 3.0 kg were divided into three groups: Sham (no drug or operation, n = 7), Control (laminectomy+single dose of 1 ml/kg saline orally, after trauma; n = 7) and RJ (laminectomy+100mg/kg RJ, orally, after trauma, n = 7). Laminectomy was perfor med at T10 and balloon catheter was applied extradurally for traumatic SCI. Four and 24h after surgery, rabbits were evaluated according to the Tarlov scoring system. Blood, cerebrospinal fluid and tissue sample from spinal cord were taken for measurements of antioxidant status or detection of apoptosis. Four hours after SCI, all animals in control or RJ treated groups became paraparesic. Significant improvement was observed in RJ treated group, 24h after SCI, with respect to control. Traumatic SCI led to increase in the lipid peroxidation and decrease enzymic or non-enzymic endogenous antioxidative defense systems, and increase in apoptotic cell numbers. RJ treatment mostly prevented lipid peroxidation and also augmented endogenous enzymic or non-enzymic antioxidative defense systems. Again, RJ treatment significantly decreased the apoptotic cell number induced by SCI.


Semi-urgent pulmonary vein isolation using cryoballoon for haemodynamically unstable atrial fibrillation storm in a patient with low cardiac output syndrome: a case report.
Atrial fibrillation and heart failure are common coexisting conditions requiring hospitalisation for heart failure and death. Pulmonary vein isolation is a well-established option for symptomatic atrial fibrillation and for atrial fibrillation concomitant with heart failure with reduced left ventricular ejection fraction. Recently, pulmonary vein isolation using cryoballoon showed non-inferiority to radiofrequency ablation with respect to the treatment of patients with drug-refractory paroxysmal atrial fibrillation. However, the effectiveness of acute-phase rhythm control by semi-urgent pulmonary vein isolation using cryoballoon in patients with haemodynamically unstable atrial fibrillation storm accompanied with low cardiac output syndrome is unclear. Herein, we present a case in which semi-urgent pulmonary vein isolation using cryoballoon was effective for acute-phase rhythm control against drug-resistant and haemodynamically unstable repetitive atrial fibrillation tachycardia accompanied with low cardiac output syndrome. A 57-year-old man was hospitalised for New York Heart Association functional class 4 heart failure with atrial fibrillation tachycardia and reduced left ventricular ejection fraction of 20% accompanied with low cardiac output syndrome-induced liver damage. The haemodynamics collapsed during atrial fibrillation tachycardia, which had become resistant to intravenous amiodarone and repeated electrical cardioversions. In addition to atrial fibrillation, atrial tachycardia and common-type atrial flutter appeared on day 3. Multiple organ failure progressed gradually due to haemodynamically unstable atrial fibrillation tachycardia storm accompanied with low cardiac output syndrome. On day 4, to focus on treatment of heart failure and multiple organ failure, semi-urgent rescue pulmonary vein isolation using cryoballoon to atrial fibrillation and cavotricuspid isthmus ablation to common-type atrial flutter were performed for acute-phase rhythm control. Soon after the ablation procedure, atrial fibrillation and common-type atrial flutter were lessened, and sinus rhythm was restored. A stable haemodynamics was successfully achieved with the improvement of hepatorenal function. The patient was discharged on day 77 without complications. This case demonstrates that acute-phase rhythm control by semi-urgent pulmonary vein isolation using cryoballoon could be a treatment option in patients with haemodynamically unstable atrial fibrillation tachycardia storm accompanied with low cardiac output syndrome, which is refractory to cardioversion and drug therapy.


Comparison of avidin and biotin levels in eggs from turkey hens with high and low hatchability records.
Levels of biotin and avidin were assayed in eggs from Small White turkey hens having 12-15 week average hatchability of fertile egg records (HF) of 13 and 99%. The median level and concentration of avidin was higher in eggs of the 13% HF (2.72 mg and 42.5 micrograms/ml, respectively) as compared with the 99% HF (1.39 mg and 23.8 micrograms/ml, respectively). Calculations for total biotin to avidin binding in the eggs revealed that all eggs in the 13% HF and residual free avidin levels after total biotin was complexed to avidin. This complex formation is expected to have limited the availability of biotin for embryonic development.


Autophagy compensates for Lkb1 loss to maintain adult mice homeostasis and survival.
Liver kinase B1 (LKB1), also known as serine/threonine kinase 11 (STK11) is the major energy sensor for cells to respond to metabolic stress. Autophagy degrades and recycles proteins, macromolecules, and organelles for cells to survive starvation. To assess the role and cross-talk between autophagy and Lkb1 in normal tissue homeostasis, we generated genetically engineered mouse models where we can conditionally delete Stk11 and autophagy essential gene, Atg7, respectively or simultaneously, throughout the adult mice. We found that Lkb1 was essential for the survival of adult mice, and autophagy activation could temporarily compensate for the acute loss of Lkb1 and extend mouse life span. We further found that acute deletion of Lkb1 in adult mice led to impaired intestinal barrier function, hypoglycemia, and abnormal serum metabolism, which was partly rescued by the Lkb1 loss-induced autophagy upregulation via inhibiting p53 induction. Taken together, we demonstrated that autophagy and Lkb1 work synergistically to maintain adult mouse homeostasis and survival.


High-resolution ultrasound in etiological evaluation of ulnar neuropathy at the elbow.
Ulnar neuropathy at the elbow (UNE) involves mechanical compression and irritation of the ulnar nerve (UN) caused by environmental and dynamic abnormalities that can however also be found in asymptomatic patients. Using high-resolution ultrasound, we aimed to assess and compare the relevance of morphological and dynamic variants of the UN and its surrounding structures (UN abnormalities) in symptomatic and asymptomatic patients. UN abnormalities in patients with UNE were assessed using high-resolution ultrasound and compared against unaffected arms (patients or healthy volunteers). We studied 234 arms of 117 individuals (89 with UNE and 145 control). Eighty-one percent of the arms with UNE compared to 40% of control (p=0.00001) showed UN abnormalities. While it was dislocated in 49% of arms with UNE compared to in 23% of control (p=0.004). The two-fold higher frequency of occurrence of UN abnormalities in arms with UNE indicates their causative or at least contributory role in such neuropathies. High-resolution ultrasound should be part of the initial evaluation of UNE in order to assess the etiology of the conflict.


Adversity, attachment and emotion recognition in BPD adolescents: the distinct roles of disengaged and controlling environment.
Literature data about emotion perception in patients with borderline personality disorders (BPD) revealed some discrepancies between some patients that are vigilant and accurate to detect their emotional environment and others that are impaired at identifying emotions of others. Even if some links between childhood adversity and facial affect recognition have been established, there is a need to understand the heterogeneous psychobiological mechanisms underlying this association. The aim is to distinguish in a BPD sample, the links between facial emotion recognition (FER) and adversity types (maltreatment and parental bonding), by evaluating two dimensions of disengaged and controlling environment. The study includes BPD adolescents (n = 45) and healthy controls (HC, n = 44): two scores of disengaged environment (parental low care; emotional and physical neglect) and controlling environment (high level of parenting control; emotional, physical and sexual abuse) were established and correlated to FER, as well as to attachment dimensions. Multiple linear regression analyzes were conducted to evaluate the effect of disengaged and controlling dimensions, on FER scores of sensitivity and accuracy, including anxious and avoidant attachment as covariables. Analyzes revealed that a disengaged environment was positively correlated to sensitivity in BPD patients, and the correlation was negative in the HC group. Controlling environment was negatively associated to accuracy of emotion in BPD. Avoidant and anxious attachment did not influence these associations. These results suggest that distinct adverse experiences account for the heterogeneity observed in emotion regulation in BPD patients.


Postoperative risks of stoma formation in patients with dementia.
Stoma formation for patients with dementia presents an increasing problem in a global ageing population. While potentially lifesaving, stomas impose significant, long-term postoperative burdens on patients, and may particularly challenge those with cognitive impairment.In this case, a patient was considered for colostomy to manage a colovesical fistula. The patient's cognitive status significantly influenced clinicians' beliefs concerning suitability for stoma formation.The relevance of dementia to stoma formation is underdiscussed within the literature. In this report, we outline the postoperative risks to which those with dementia undergoing stoma formation are particularly vulnerable. These include increased risk of psychological harm, of relocation to a nursing home, and of stoma-related complications.We hope an increased appreciation of these postoperative challenges will inform decisions concerning suitability for stoma formation in this patient group.


Causes of mortality and parasites and incidental lesions in harbour porpoises (Phocoena phocoena) from British waters.
Detailed post mortem examinations were carried out on 41 harbour porpoises (Phocoena phocoena) found dead on the coast of the United Kingdom. The commonest causes of death were entanglement in fishing gear, and parasitic and bacterial pneumonia. Among the non-fatal conditions parasitoses of various organs were common and there was a very wide variety of other conditions. In total 295 diseases and other lesions were found, an average of 7.2 per animal.


Mesencephalic projections to the facial nucleus in the cat. An autoradiographical tracing study.
In 33 cats the projections of different parts of the mesencephalon to the facial nucleus were studied with the aid of the autoradiographical tracing method. The results indicate the existence of many different mesencephalo-facial pathways. The dorsomedial facial subnucleus, containing motoneurons innervating ear muscles, receives afferents from 4 different mesencephalic areas: a, the most rostral mesencephalic reticular formation; b, the nucleus of Darkschewitsch and/or the ventral part of the rostral PAG; c, the interstitial nucleus of Cajal and/or the mesencephalic tegmentum dorsomedial to the red nucleus. These areas project bilaterally by way of an ipsilateral medial tegmental pathway. The medial part of the deep tectum. This area projects bilaterally by way of the tecto-spinal tract. The lateral mesencephalic tegmentum close to the parabigeminal nucleus. This area projects mainly contralaterally by way of a separate contralateral lateral tegmental fiber bundle. The mesencephalic tegmentum just dorsolateral to the red nucleus and perhaps from the dorsolateral red nucleus itself. This area projects contralaterally by way of the rubrospinal tract. The intermediate facial subnucleus containing motoneurons innervating the muscle around the eye, receives afferents from two different mesencephalic areas: The dorsal part of the rostral as well as caudal red nucleus (but not from its caudal pole) and from the dorsally adjoining mesencephalic tegmentum including the area of the nucleus of Darkschewitsch and the interstitial nucleus of Cajal. These areas project contralaterally by way of the contralateral rubrospinal tract. The nucleus of the optic tract and/or the olivary pretectal nucleus. This area projects contralaterally by way of a contralateral medial tegmental pathway. The lateral and ventrolateral facial subnuclei containing motoneurons innervating the muscles around the mouth receive afferents from two different mesencephalic areas: The lateral part of the deep tectal layers. This area projects contralaterally by way of the tecto-spinal tract. The nucleus raphe dorsalis and perhaps the nucleus centralis superior. This area projects by way of the lateral tegmentum of caudal pons and medulla.


Monopolar transurethral resection of the prostate using water as the irrigation fluid: Our initial experience.
Monopolar transurethral resection of the prostate (M-TURP) has been the gold standard of surgical intervention in patients with benign prostatic hyperplasia with the indication for surgery. This can be achieved using varieties of irrigation fluids. To document our experience with M-TURP using water as irrigation fluid in 123 consecutive patients. A retrospective study of all patients who had M-TURP with water as irrigation fluid was performed between January 2017 and July 2019. Information retrieved from theatre records and case notes includes patient's socio-demographic data, indications for surgery, intra-operative findings, the volume of resected chips and irrigation fluid used, post-operative complications and patient's satisfaction with the outcome of the procedure. These data were analysed using SPSS version 23. Data from 123 patients were analysed and presented. The age range was 44-96 years with a mean of 69 years. Prostate volume ranges from 13.9 to 276.00 mls with a mean of 95.69 mls while resected prostate volume ranges from 2.0 to 158.0 mls with a mean of 56.68 mls. Volume of the sterile water used as irrigation fluid ranged from 5.0 L to 174.0 L with a mean of 68.7 L. Mean reduction in International Prostate Symptoms Score, improvement in Q-max and reduction in post-void residual urine were 22.1, 16.9 and 141.6 mls, respectively. Transfusion rate was 6.5% while the duration of admission ranges from 1 to 6 days, with a mean of 2.5 days. The overall complication rate was 26.0%. Ninety-six percent were satisfied with the outcome. M-TURP using water as irrigation fluid is safe and is as good as using the more rather expensive glycine or normal saline in bipolar TURP.


Association between sleep duration and albumin in US adults: a cross-sectional study of NHANES 2015-2018.
Albumin has multiple functions and is used in the clinical assessment of liver function, kidney function and nutritional status. However, few epidemiological studies have evaluated the association between sleep duration and albumin. Therefore, we carried out a cross-sectional study to address this issue. The aim of the study was to investigate the association between sleep duration and albumin in American adults based on the NHANES (National Health and Nutrition Examination Survey). A total of 9,973 participants aged [Formula: see text] 20 years were included in this study from NHANES 2015-2018. Weighted data were calculated according to analytical guidelines. Linear regression models and smooth curve fitting were used to assess and describe the relationship between sleep duration and albumin. The inflection point was determined by a two-step recursive method. Moreover, univariate and stratified analyses were performed. There was an inverted U-shaped association between sleep duration and albumin levels. Albumin levels were highest when the sleep duration was 7.5 h. Compared to 7-8 h of sleep, short sleep duration was linked to lower albumin levels [sleep duration [Formula: see text] 5 h: β [Formula: see text]-1.00, 95% CI (-1.26, -0.74), P < 0.0001]. Compared to 7-8 h of sleep, long sleep duration was related to lower albumin levels [sleep duration [Formula: see text] 9 h: β [Formula: see text] -0.48, 95% CI (-0.68, -0.27), P < 0.0001]. Sleep duration had an inverted U-shaped relationship with albumin, with short or long sleep duration associated with significantly lower albumin levels.


Within-colony genetic diversity differentially affects foraging, nest maintenance, and aggression in two species of harvester ants.
There is accumulating evidence that genetic diversity improves the behavioral performance and consequently the fitness in groups of social animals. We examined the behavioral performance of colonies of two co-occurring, congeneric harvester ant species (Messor arenarius and a non-described Messor sp.) in fitness-related behaviors, pertaining to foraging performance, nest maintenance, and aggression. We linked these behaviors to the colonial genetic diversity, by genotyping workers, using six and five microsatellite markers for M. arenarius and M. sp., respectively. Correlations of genetic diversity with colony performance and aggression level contrasted between the two species. In M. arenarius, genetic diversity was correlated with foraging performance and nest maintenance but not with the overall aggression level, while in M. sp., genetic diversity was correlated with the overall aggression level, but not with foraging performance or nest maintenance. The two species exhibited similar specific aggression levels, with higher aggression shown towards heterospecifics and lower towards non-nestmate conspecifics and nestmates. However, M. sp. workers displayed a tendency to interact for longer with heterospecifics than did M. arenarius. We speculate that the different foraging strategies, group vs. individual foraging, and possibly also the different mating systems, contribute to the differences found in behavior between the two species.


Peri-operative outcome for day-case laparoscopic and open inguinal hernia repair.
This study documents the results obtained in 30 day patients undergoing open hernia repair under local infiltration block with patient-controlled sedation (group A) and 29 day patients undergoing laparoscopic hernia repair under general anaesthesia (group B). The mean operating time was less in group A (44.8 min) compared with group B (66.6 min) (p < 0.0001). Similarly, stage 1 recovery room times were longer in group B (98.1 min) than group A (45.1 min) (p < 0.0001). Time to discharge for group A (139.1 min) was significantly shorter than group B (224.2 min) (p < 0.002), with more peri-operative complications occurring in group B and greater analgesic requirements. An open inguinal hernia repair under local infiltration block is the optimal approach for unilateral non-recurrent herniae as a day surgical procedure. These results have important cost and efficiency implications.


CD133-induced TM4SF5 expression promotes sphere growth via recruitment and blocking of protein tyrosine phosphatase receptor type F (PTPRF).
CD133 is a surface marker of liver cancer stem cells. Transmembrane 4 L six family member 5 (TM4SF5) promotes sphere growth and circulation. However, it is unknown how CD133 and TM4SF5 cross-talk with each other for cancer stem cell properties. Here, we investigated the significance of inter-relationships between CD133, TM4SF5, CD44, and protein tyrosine phosphatase receptor type F (PTPRF) in a three-dimensional (3D) sphere growth system. We found that CD133 upregulated TM4SF5 and CD44, whereas TM4SF5 and CD44 did not affect CD133 expression. Signaling activity following CD133 phosphorylation caused TM4SF5 expression and sphere growth. TM4SF5 bound to CD133 and promoted c-Src activity for CD133 phosphorylation as a positive feedback loop, leading to CD133-mediated sphere growth that was inhibited by TM4SF5 inhibition or suppression. TM4SF5 also bound PTPRF and promoted paxillin phosphorylation. Decreased sphere growth upon CD133 suppression was recovered by TM4SF5 expression and partially by PTPRF suppression. TM4SF5 inhibition enhanced PTPRF levels and abolished PTPRF suppression-mediated sphere growth. Altogether, CD133-induced TM4SF5 expression and function were important for liver cancer sphere growth and may be a promising target to block metastasis.


Application of Supervised Machine Learning Techniques to Forecast the COVID-19 U.S. Recession and Stock Market Crash.
Machine learning (ML), a transformational technology, has been successfully applied to forecasting events down the road. This paper demonstrates that supervised ML techniques can be used in recession and stock market crash (more than 20% drawdown) forecasting. After learning from strictly past monthly data, ML algorithms detected the Covid-19 recession by December 2019, six months before the official NBER announcement. Moreover, ML algorithms foresaw the March 2020 S&P500 crash two months before it happened. The current labor market and housing are harbingers of a future U.S. recession (in 3 months). Financial factors have a bigger role to play in stock market crashes than economic factors. The labor market appears as a top-two feature in predicting both recessions and crashes. ML algorithms detect that the U.S. exited recession before December 2020, even though the official NBER announcement has not yet been made. They also do not anticipate a U.S. stock market crash before March 2021. ML methods have three times higher false discovery rates of recessions compared to crashes.


The effect of dimethyl sulfoxide on cholesterol and bile acid metabolism in rats.
The effect of DMSO on cholesterol and bile acid metabolism was studied in rats. Male Sprague-Dawley rats were randomly assigned to one of two groups and given either tap water or 2% DMSO (v/v) in tap water to drink for 9 days. Both food (stock rat diet) and water were available ad libitum. Animals in both groups gained weight equally throughout the study. They also had similar liver weights (g/100 g body wt) at the end of the study (control: 5.0 +/- 0.1 (N = 6) vs DMSO: 4.9 +/- 0.1 (N = 6]. The activity of hepatic cholesterol 7 alpha-hydroxylase (pmole/mg/min), the rate-limiting enzyme of bile acid biosynthesis, was significantly (P less than 0.005) reduced in the treated animals (control: 9.7 +/- 1.0 (N = 6) vs DMSO: 4.3 +/- 0.7 (N = 6)). Plasma cholesterol (mg/dl) was significantly (P less than 0.005) elevated in the treated animals (control: 90 +/- 3 (N = 6) vs DMSO: 107 +/- 4 (N = 6)), a finding consistent with the reduced CH-7 alpha hydroxylase activity in this group. DMSO treatment did not affect either microsomal cholesterol content or hepatic glutathione content. Thus, this study has shown that DMSO treatment per se can affect cholesterol and bile acid metabolism. However, the precise mechanisms whereby DMSO exerts the observed effects are not known.


Drug-induced cardiovascular disorders.
As the variety and range of pharmaceutical agents available to the medical profession continues to expand, one unavoidable effect will be an increase in drug-induced disease, including cardiovascular disorders. However, given the high rates of cardiovascular disease and prevalence of recognised cardiovascular risk factors in the population, it is sometimes impossible to conclusively attribute any individual patients' ill health to one particular drug. As a result, the relationship between drugs and cardiovascular disease is often difficult to quantify. This review discusses specific forms of drug-induced cardiovascular disease such as heart failure, left ventricular systolic dysfunction, hypertension and arrhythmia. Suspected culprit drugs for all disorders are highlighted. Specific attention is given to certain drug groups with a strong association with one or more forms of cardiovascular disease: these include anthracyclines, antipsychotics, NSAIDs and cyclo-oxygenase 2 inhibitors. Additionally, advice is offered on how physicians might distinguish drug-induced cardiovascular disorders from other aetiologies.


Baby's first bath: Changes in skin barrier function after bathing full-term newborns with water vs liquid baby cleanser.
The impact of the newborn's first bath, whether given with water alone or water with skin cleansing products, on skin barrier function is unknown. We evaluated skin barrier function, measured by skin surface pH (primary outcome), transepidermal water loss (TEWL), and hydration of the stratum corneum (SCH) in 100 newborns before and after their first bath, randomizing this cohort to bathing with water alone or with water and a liquid baby cleanser. Two consecutive measurements of each parameter were obtained at two anatomic locations, the volar forearm, and below the sternum. Randomization was by mode of delivery, with 50 vaginal and 50 cesarean section (C/S) delivered newborns. Skin pH decreased significantly following the first bath at both anatomic sites regardless of whether the bath was performed with water or with cleanser, and there was no significant effect on the change in pH in these two groups. Baseline TEWL and SCH measurements were significantly lower in the sternum area compared to the volar forearm. TEWL decreased significantly after the first bath except when the bath was given with water alone on the sternum site. SCH also decreased significantly after the first bath except in the forearm when the bath was given with water alone. We conclude that skin surface pH, TEWL, and SCH all decrease significantly following the first bath, an indication of the development of skin barrier function in the newly born infant. In addition, bathing with water alone or water and a liquid baby cleanser does not impact the developing skin barrier.


Epidemiology and prevention of cervical cancer in Indonesia, Malaysia, the Philippines, Thailand and Vietnam.
Cervical cancer remains one of the leading causes of cancers in women from Indonesia, Malaysia, the Philippines, Thailand and Vietnam. High-risk human papillomavirus (HPV) types, particularly HPV-16 and 18, are consistently identified in cervical cancer cases regardless of geographical region. Factors that have been identified to increase the likelihood of HPV exposure or subsequent development of cervical cancer include young age at first intercourse, high parity and multiple sexual partners. Cervical cancer screening programs in these countries include Pap smears, single visit approach utilizing visual inspection with acetic acid followed by cryotherapy, as well as screening with colposcopy. Uptake of screening remains low in all regions and is further compounded by the lack of basic knowledge women have regarding screening as an opportunity for the prevention of cervical cancer. Prophylactic HPV vaccination with the quadrivalent vaccine has already been approved for use in Malaysia, the Philippines and Thailand, while the bivalent vaccine has also been approved in the Philippines. However, there has been no national or government vaccination policy implemented in any of these countries.


Immune response and protection of cattle and pigs generated by a vaccinia virus recombinant expressing the F protein of rinderpest virus.
The immune response of cattle and pigs to a vaccinia recombinant virus containing the fusion (F) protein gene of rinderpest virus was examined. Half the cattle and all the pigs gave humoral response to primary vaccination and all the cattle gave an anamnestic response to a second vaccination 28 days after the primary vaccination. All the cattle after a single or secondary vaccination were completely protected clinically after exposure to a lethal dose of the Saudi 1/81 strain of virus. Prior vaccination with another TK- vaccinia recombinant (VVCAT) suppressed, but did not abrogate, the immune response to the rinderpest F recombinant. The pigs gave a humoral immune response in the absence of any local reaction at the site of vaccination.


Effect of charge ratio on lipoplex-mediated gene delivery and liver toxicity.
The vast majority of studies investigating gene delivery have utilized cationic delivery vehicles, but anionic nanoparticles can also possess high transfection activity, and offer significant benefits in terms of ease of preparation and reduced toxicity. Our study on lipoplexes possessing cholesterol nanodomains demonstrates that in vitro transfection after exposure to serum can be high at anionic charge ratios, and that this effect is also evident in studies assessing delivery to tumors in vivo, despite reduced circulation times. In addition, accumulation in the liver and lungs is reduced as compared with lipoplexes formulated at cationic charge ratios. Lipoplexes prepared at anionic charge ratios offer comparable tumor delivery and reduced liver toxicity despite shorter circulation times.


Enantioselectivity of some 1-(benzofuran-2-yl)-1-(1-H-imidazol-1-yl) alkanes as inhibitors of P450Arom.
The low stereospecificity of the enantiomers of 1-[(benzofuran-2-yl)-4-chlorophenylmethyl]imidazole (6, R=H, R'=4'-Cl) and the corresponding 4-fluoro compound as inhibitors of aromatase (P450Arom) has been explored using 1-(5,7-dichlorobenzofuran-2-yl)-1-(1H-imidaz-1-yl)ethane (7, R1=R2=Cl, R=CH3), -propane (7, R1=R2=Cl, R=C2H5), and the corresponding 5,7-dibromo compounds resolved as their dibenzoyl-D (or -L) tartrates. Low enantioselectivity ratios of 4.8 (5,7-diCl) and 12.6 (5,7-diBr) were shown for the ethanes. The values for the corresponding propanes were 8.3 and 5.2, respectively, and for these compounds the stereoselectivity was reversed.


[Unilateral paralysis of the lower cranial nerves caused by lesion of the internal carotid artery].
We report two cases of unilateral, isolated lower cranial nerves (IX, X, XI and XII) palsy: both were due to a lesion of the internal carotid artery in the para-pharyngeal space (a dissection and a pseudoaneurysm). The diagnosis was based upon magnetic resonance imaging and selective angiography. The normality of the external carotid artery on angiography led to the hypothesis of a direct compression of the lower cranial nerves in the para-pharyngeal space, rather than an ischemia of these nerves.


Laparoscopic identification of combined pediatric femoral hernia and ruptured abdominal cyst of the canal of Nuck: A report of an extremely rare case.
A 7-year-old girl was referred to our hospital with a suspected right-sided indirect inguinal hernia. An egg-sized elastic, non-painful mass was palpated in the right inguinal region. Preoperative CT demonstrated a 30-mm simple cystic mass in the right internal inguinal canal, which we diagnosed as an abdominal cyst of the canal of Nuck. Laparoscopy revealed that the abdominal cystic component was ruptured, so we performed Pott's procedure. However, the patient's right groin swelled on postoperative day 3, necessitating re-operation. The patient's symptoms recurred again after 3 months, despite having had two surgical repairs. In the third operation, a right-sided femoral hernia was confirmed and repaired via external and laparoscopic approaches. To the best of our knowledge, there have been no reports on the combination of femoral hernia and cyst of the canal of Nuck in children. A laparoscopic approach was useful for obtaining a definitive diagnosis and conducting a safe and secure surgical repair.


FTY720 (fingolimod) increases vascular tone and blood pressure in spontaneously hypertensive rats via inhibition of sphingosine kinase.
FTY720 (Fingolimod) is a recently approved orally administered drug for the treatment of multiple sclerosis. Phase II and III clinical trials have demonstrated that this drug modestly increases BP. We previously showed that inhibition of sphingosine kinase increases vascular tone and BP in hypertensive, but not normotensive rats. Since FTY720 is reported to have inhibitory effects on sphingosine kinase, we investigated whether FTY720 increases vascular tone and BP only in hypertensive rats via this mechanism. The contractile and BP modulating effects of FTY720 were studied in vivo and ex vivo (wire myography) in age-matched normotensive Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Oral administration of FTY720 induced an increase in mean arterial pressure in SHR, whereas a decrease in BP was observed in WKY rats, as measured 24 h after administration. Similar to the sphingosine kinase inhibitor dimethylsphingosine (DMS), FTY720 induced large contractions in isolated carotid arteries from SHR, but not in those from WKY. In contrast, the phosphorylated form of FTY720 did not induce contractions in isolated carotid arteries from SHR. FTY720-induced contractions were inhibited by endothelium denudation, COX and thromboxane synthase inhibitors, and by thromboxane receptor antagonism, indicating that (like DMS-induced contractions) they were endothelium-dependent and mediated by thromboxane A₂. These data demonstrate that FTY720 increases vascular tone and BP only in hypertensive rats, most likely as a result of its inhibitory effect on sphingosine kinase.


Cardiogenic shock in ACS. Part 2: Role of mechanical circulatory support.
This Review explores contemporary circulatory support in profound postinfarction cardiogenic shock. Frequently, death is the only alternative to implantation of a blood pump, so prospective randomized trials of device versus medical treatment are unacceptable and evidence is derived from clinical experience. Irrespective of ACC/AHA and European guidelines, no study has shown survival benefit for the intra-aortic balloon pump in patients with established shock. In the past 10 years, the safety and durability of mechanical blood pumps has improved considerably. New temporary and long-term rotary pumps have transformed outcomes for patients with acute heart failure. For urgent resuscitation, outreach salvage, and transportation extracorporeal membrane oxygenation (ECMO) is a reliable, but time limited, first step. ECMO decompresses the venous system, provides flow, and ensures oxygenation, but does not unload the failing left ventricle. Myocardial stunning takes days, and sometimes weeks, to recover. Effective ventricular unloading is best achieved by surgical implantation of a temporary rotary or volume-displacement pump. After cardiopulmonary resuscitation, hemodynamic stabilization allows assessment of cerebral injury and prognosis. Published series demonstrate that 50-75% of patients with profound shock can be salvaged either through native heart recovery, urgent transplantation, or switch to a long-term pump.


[Lobular carcinoma of the breast with neuroendocrine differentiation. Study of a case].
A breast tumor with morphologic features of neuroendocrine differentiation and containing large amounts of estrogen receptor protein was associated with areas of typical infiltrating lobular carcinoma. The neuroendocrine areas were argyrophilic, NSE positive and ultrastructurally did not show dense granules. Results of flow cytometric analysis revealed aneuploid nuclear DNA.


Comparison of several lizard Leishmania species and strains in terms of kinetoplast minicircle and maxicircle DNA sequences, nuclear chromosomes, and membrane lipids.
Eight strains of a lizard Leishmania species, L. tarentolae, were compared with four other saurian species [L. hoogstrali, L. adleri, L. agamae and Leishmania sp. LizS], with L. major from man and with Trypanosoma platydactyli, a putative lizard trypanosome, in terms of kinetoplast DNA minicircle and maxicircle sequences and in terms of nuclear chromosome patterns on orthogonal gel electrophoresis. The L. tarentolae strains fell into two major groups, one (group A) consisting of the L. tarentolae strains, UC, Krassner and Trager, derived from an Algerian gecko isolate and the other (group B) consisting of five L. tarentolae LEM strains isolated from geckos in southern France. T. platydactyli TPCL2, which was postulated by Wallbanks et al. to represent the lizard form of a French L. tarentolae strain, was closely related to the UC strain and not to the LEM strains, in all respects analyzed. Leishmania sp. LizS from a Mongolian gecko and L. hoogstrali from a Sudanese gecko showed some sequence similarities to the L. tarentolae strains, but the leishmanias said to be L. adleri from a Kenyan lacertid and L. agamae from an Israeli agamid showed no minicircle sequence similarities with lizard Leishmania and in fact were probably the same species. The maxicircle divergent region was larger in the group B strains than in the group A strains, but there were sequences in common with both groups, and not with L. hoogstrali and L. major. Four strains of L. tarentolae, the four other supposed saurian Leishmania species, three mammalian leishmanias, T. platydactyli and four other trypanosomes, T. cyclops (Malaysian macaque), T. conorrhini (Hawaiian reduviid bug), T. cruzi (man) and T. lewisi (feral rat) were analyzed for their contents of sterols and phosphoglyceride fatty acyl groups. T. platydactyli TPCL2 contained a sterol (5-dehydroepisterol), a phosphatidylcholine fatty acyl group (alpha-linolenic acid) and a phosphatidylethanolamine fatty acyl group (dihydrosterculic acid) characteristic of members of the genus Leishmania and not the genus Trypanosoma. The proportions of those lipids in the free sterol and phosphoglyceride fractions of T. platydactyli TPCL2 most closely resembled those seen in the Leishmania strains from Algerian, French, Mongolian and Sudanese geckos.


Bm Delta-pgm, a vaccine for the control of Brucella melitensis with cross-species protective properties.
Brucellosis remains one of the most worldwide distributed zoonosis inflicting serious economical and human health problems in many areas of the world. The disease is caused by different species of the genus Brucella that have different tropisms towards different mammals being the most relevant for human health Brucella abortus, Brucella melitensis and Brucella suis that infect cows, goats/sheep, and swine respectively. For B. melitensis, considered the species with more zoonotic potential and highly aggressive for animals, only one vaccine is available to date in the market: Rev 1. This attenuated strain has the disadvantage that is has a very high residual virulence for animals and humans and, for this reason, it is applied by ocular instillation which is technically challenging in many productive settings. For this reason, the search for new vaccines for caprine and ovine brucellosis is an active topic of research. We describe here the construction of a novel highly attenuated vaccine strain (Bm Delta-pgm) that confers excellent levels of protection against B. melitensis in the mouse model of infection. This strain is a clean deletion of the phosphoglucomutase (pgm) gene that codes for a protein that catalyzes the conversion of glucose-6-P to glucose-1-P, which is used as a precursor for the biosynthesis of many polysaccharides, including the O-antigen of the lipopolysaccharide and cyclic beta glucans. Our results indicate that vaccination with Bm Delta-pgm induces a robust memory cellular immune response but no antibody production against the O-antigen. Cross protection experiments show that this new vaccine protects against B. abortus and B. suis raising the possibility that Bm Delta-pgm could be used as a universal vaccine for the most important Brucella species.


Prognosis in stable angina pectoris and silent myocardial ischemia.
The results of current investigation suggest that a former clinical standby, namely, the presence or absence of angina, is no longer the principal prognostic factor for determining a patient's risk of cardiac events, including myocardial infarction. In a retrospective analysis, patients with chronic stable angina were compared on the basis of presence or absence of angina during ischemia detected by thallium imaging. Patients were similar in terms of risk factors, clinical characteristics and catheterization data. At 30 months of follow-up, the myocardial infarction rate was 22% in the silent group compared with 4% in the group with angina. Transient asymptomatic ischemia has prognostic value independent of other variables such as exercise stress testing or cardiac catheterization data. Future prognostic studies should be careful to include patient populations with similar characteristics; they also will need to provide protracted follow-up and utilize sensitive and reproducible diagnostic techniques.


Identification and distribution of axonal dystrophic neurites in Alzheimer's disease.
Dystrophic neurites (DNs) are one of the neuropathological characteristics of Alzheimer's disease (AD). Previously, it has been suggested that tau-immunoreactive DNs are of dendritic origin and that axonal and dendritic dystrophic neurites are morphologically indistinguishable. In the present study, two monoclonal antibodies, tau-1 and PHF-1, were used to examine sections of the hippocampal formation from AD and normal aged brains. Both antibodies stained dendritic DNs as well as axonal DNs. Axonal DNs were clearly seen in axonal fiber tracts, white matter and hippocampal terminal regions. Axonal DNs arising from neurofibrillary tangles were easily detected in CA3 and CA1. The morphological appearance of axonal DNs varied with the neuron type from which it originated. The most distinctive feature of tau-1 or PHF-1 immunostained axonal DNs was their uneven contour, alternating swollen and shrunken segments and short rod or cone shaped fragments. In contrast, dendritic dystrophic neurites are thicker and more tortuous. It appears that while DNs are both dendritic and axonal in origin, axonal DNs are more prevalent and widespread in the AD brain than previously realized and may represent one of the main pathological lesions in AD.


Nonunion of the capitate: a case report.
A patient with nonunion of the capitate presented for treatment with a painful, snapping wrist. Grafting was successful in obtaining union of the fracture and relief of symptoms.


Preparation of thrombin-loaded calcium alginate microspheres with dual-mode imaging and study on their embolic properties in vivo.
Transcatheter arterial embolization (TAE) has played a huge role in the interventional treatment of organ bleeding and accidental bleeding. Choosing bio-embolization materials with good biocompatibility is an important part of TAE. In this work, we prepared a calcium alginate embolic microsphere using high-voltage electrostatic droplet technology. The microsphere simultaneously encapsulated silver sulfide quantum dots (Ag2S QDs) and barium sulfate (BaSO4), and fixed thrombin on its surface. Thrombin can achieve an embolic effect while stopping bleeding. The embolic microsphere has good near-infrared two-zone (NIR-II) imaging and X-ray imaging effects, and the luminous effect of NIR-II is better than that of X-rays. This breaks the limitations of traditional embolic microspheres that only have X-ray imaging. And the microspheres have good biocompatibility and blood compatibility. Preliminary application results show that the microspheres can achieve a good embolization effect in the ear arteries of New Zealand white rabbits, and can be used as an effective material for arterial embolization and hemostasis. This work realizes the clinical embolization application of NIR-II combined with X-ray multimodal imaging technology in biomedical imaging, achieving complementary advantages and excellent results, more suitable for studying biological changes and clinical applications.


Lipid peroxidation in tumour cells.
Several studies point to the existence of a disturbance in the metabolism of the reactive species of oxygen in cancer cells. Based on this evidence, and in particular on a characteristic behaviour of tumour membrane lipids, namely their growth-related resistance to oxy-radical-induced peroxidation, a sequence of events is outlined that could hypothetically drive the transformed cell to an uncontrolled proliferation. The proposed scheme is also conceived as a framework for further in vivo investigations of the complex biological phenomena of tumour cell growth and invasion in more integrated and kinetically controlled cellular systems.


Switching from Tenofovir Disoproxil to Tenofovir Alafenamide Fumarate: Impact on Cardiovascular Risk and Lipid Profile in People Living with HIV, an Observational Study.
In the era of combination antiretroviral therapy (ART), people living with HIV (PLHIV) still face an increased risk of cardiovascular disease (CVD). Tenofovir alafenamide fumarate (TAF) is superior to its precursor tenofovir disoproxil fumarate (TDF) regarding bone and renal toxicity, but there are concerns about a negative effect on lipid profile. This observational, single-center study investigates the effects on lipid profile and cardiovascular (CVD) risk of the switch from TDF to TAF, in combination with emtricitabine/elvitegravir/cobicistat (FTC/EVG/c), in patients with no exposure to other antiretrovirals. Routine laboratory measurements, somatometric characteristics, and smoking status were analyzed for the assessment of CVD risk changes, using D:A:D and ATP III scores pre- and postswitch. A total of 62 patients with a mean age of 32.9 years were included in this study. Sixty-one patients (98.4%) were men, 38 (61.3%) late presenters, and 39 (62.9%) active smokers. A year after the switch, there was a significant increase in total cholesterol (178 ± 38 to 194 ± 40 mg/dL, p < .001), high-density lipoprotein (45 ± 12 to 48 ± 13 mg/dL, p = .001), and low-density lipoprotein (117 ± 32 to 137 ± 36 mg/dL, p < .001). Mean increase of the 10-year D:A:D score was 1.13% (95% confidence interval, 1.05-1.22, p = .002). Changes were more prominent in nonsmokers. Body mass index and average weight showed an upward trend. Switching from TDF to TAF caused significant changes in lipid profile at 14 months of follow-up, in young, otherwise healthy PLHIV. CVD risk, as measured by D:A:D, showed a statistically significant increase, but more data are needed to determine clinical significance. These results point toward a patient-centered approach when selecting an ART regimen.


The effect of age on hepatic gene transfer with self-inactivating lentiviral vectors in vivo.
It is known that cellular proliferation, by either compensatory regeneration or direct hyperplasia, can augment lentiviral vector transduction into hepatocytes in vivo. For this reason, the present study was designed to determine if adolescent mice (312 weeks of age), which still have relatively proliferating livers, would have differential transduction compared to older (7 weeks of age) mice. Self-inactivating lentiviral vectors containing the human alpha(1)-antitrypsin (hAAT) promoter driving the expression of either the bacterial lacZ gene or the hAAT cDNA were generated for these studies. We found that adolescent mice given lentiviral vectors expressing lacZ (50 micro g p24/mouse) via intravenous administration had a significantly higher level of hepatocyte transduction as measured by X-gal staining of liver sections compared to the 7-week-old mice. In addition, serum hAAT levels were nearly 40-fold higher in 312-week-old mice administered lentiviral vectors expressing hAAT (50 micro g p24/mouse) compared to the 7-week-old mice. Moreover, the incorporation of a matrix attachment region from immunoglobulin kappa significantly increased transduction of hepatocytes in vivo. Although there was a small reduction in the circulating levels of hAAT, likely due to an immune response against the transgene product, gene expression was sustained for the duration of the study (30 weeks in total). In conclusion, the present study strongly demonstrates that lentiviral vector transduction efficiency and transgene expression were significantly enhanced in adolescent compared to older mice.


Comparison of pathogens and antibiotic resistance of burn patients in the burn ICU or in the common burn ward.
This study aims to compare pathogens and their antibiotic resistances of burn patients from burn intensive care unit (ICU) or common burn ward. Of 2395 clinical samples from 63 patients in burn ICU, pathogens were detected in 1621 samples, in which 1203 strains (74.2%) were Gram negative bacteria, 248 strains (15.3%) were Gram positive bacteria, 170 strains (10.5%) were fungi. Top-4 microorganisms isolated from patients in burn ICU were Bauman's Acinetobacter (557, 34.4%), Pseudomonas aeruginosa (287.17.7%), Staphylococcus aureus (199, 12.3%) and Klebsiella pneumoniae (171, 10.5%). Of 512 clinical samples from 235 patients in common burn units, pathogens were detected in 373 samples, in which 189 (50.6%) strains were Gram negative bacteria, 150 strains (40.2%) were Gram positive bacteria, 34 strains (9.2%) were fungi. Top-4 microorganisms isolated from patients in common burn units were S. aureus (103, 27.6%), P. aeruginosa (46, 12.3%), K. pneumoniae (38, 10.2%) and Escherichia coli (32, 8.6%). Antibiotic resistance rates of pathogens isolated from clinical samples of burn patients from ICU was significantly higher than those from common units. Pathogens and their antibiotic resistances are significantly different between burn ICU and common burn units. This finding has great implication for infection control in burn patients.