Integration of Gross Anatomy, Histology, and Pathology in a Pre-matriculation Curriculum: A Triple-Discipline Approach.
In recent years, many schools have cut back on their teaching and laboratory hours, and courses in the anatomical sciences are more integrated into the horizontal and longitudinal curriculums. Traditionally, teaching in anatomical science classes consists of lectures and laboratory sessions. Usually, gross anatomy and histology are the two main courses in pre-matriculation programs. The summer pre-matriculation program at the University of Mississippi Medical Center (UMMC) was designed to better prepare students for success in their first year of medicine and dentistry. The course provided these students with an opportunity to study gross anatomy and histology ahead of time and develop their learning skills for the coming academic year. Historically, gross anatomy and histology courses have been taught separately with a different emphasis. We have designed a new approach to implement gross anatomy, histology, and pathology-all three disciplines-in a single lecture in the organ section of the histology course. This triple-discipline (triple lecture) approach allows three professors in anatomy, histology, and pathology to work together in a two-and-a-half-hour review lecture. This approach allows students to develop their critical thinking skills and better prepares them to transfer basic anatomic knowledge into their future clinical practice. Students indicated this was their first experience with the triple-discipline approach, and they remarked that it helped them integrate anatomy and histology as well as demonstrate the clinical importance of the structures and organs. This approach can be used at different stages of medical education and helps faculty and students better integrate various disciplines and is more suitable in the modern curriculum. A similar approach was used in our fourth year course in medical histology.


Synthesis, crystal structure and second-order nonlinear optical property of a novel pentanary selenide (K3I)[InB12(InSe4)3].
A novel pentanary selenide (K3I)[InB12(InSe4)3] was obtained via a high-temperature solid-state method. It crystallizes in the hexagonal space group P6322 which features an InSe4 tetrahedron consolidated B12 icosahedron and 1-D chain constructed by InSe6 octahedron and B12Se12 cluster alternatively connected along the c-axis. Second-order nonlinear optical property measurement shows that it is second harmonic generation-active. Theory calculation indicates that it is an indirect semiconductor with the energy gap of 1.15 eV.


The good character at work: an initial study on the contribution of character strengths in identifying healthy and unhealthy work-related behavior and experience patterns.
Positive psychological functioning has been related to various positive work-related outcome variables, such as job satisfaction or work engagement. The aim of the present study was to examine the relations between morally positively valued traits (i.e., strengths of character) and work-related behaviors. A sample of 887 adult women completed the Values in Action Inventory of Strengths (VIA-IS) and the Work-related Behavior and Experience Patterns Questionnaire (AVEM) in an online survey. Those assigned to healthy work-related behavior and experience patterns differed in their strengths profiles from those that demonstrated unhealthy patterns (i.e., burnout type) in a predictable way. Especially the strengths of zest, persistence, hope, and curiosity seemed to play a key role in healthy and ambitious work behavior. The study underlines the relevance of character strengths in work settings and suggests that interventions based on character strengths could substantiate interventions already existing at the workplace in order to enhance positive work outcomes further (e.g., work satisfaction, engagement).


Cardiac point of care testing: a focused review of current National Academy of Clinical Biochemistry guidelines and measurement platforms.
Cardiac markers are a cornerstone for assessment of suspected acute coronary syndrome (ACS) patients. The National Academy for Clinical Biochemistry has recently developed practice guidelines for clinical, analytical and point-of-care (POC) testing in the context of ACS. Several technologies have become available for POC applications. Cardiac troponin is the preferred biochemical marker for diagnosis, risk stratification and guiding management of suspected ACS patients. Samples must be collected with proper timing, typically on presentation and then 6 to 9 h later. Assays should work toward a goal of total CV <10% at the 99th percentile cutpoint, and should adhere to specifications defined by professional organizations. A 1-h or less turnaround time is specified; quantitative POC testing should be implemented if this timing cannot be met consistently by the central laboratory. The same quality criteria for assays apply regardless of testing venue. IMPLEMENTATION/MANAGEMENT: Laboratory medicine personnel must have active role in implementation, choice of technology and management of POC cardiac marker testing. Cardiac troponin measurements at POC are a viable alternative when testing needs cannot be met by the central laboratory. Laboratory medicine must be involved in implementation and ongoing service. Quality of testing must not be compromised by performance at POC.


[Hyperthyroidism and atrioventricular heart block (author's transl)].
Two cases of thyrotoxicosis including a first-degree heart block are reported; a study of action potentials of the bundle of His was achieved in the second case. The association atrioventricular block-hyperthyroidism is unusual but does not seem to be a pure coincidence. The direct effect of thyroid hormon on the myocardium is supposed to be responsible for the conduction disturbance; its disappearance with the cure of the thyrotoxicosis is a favourable argument for a relation of causality. The therapeutic consequence of this association is to exclude completely the use of betablockers.


Policies and practices for the clinical management of HIV/HCV coinfected children in Europe: an epidemiological survey.
The antenatal prevalence of HIV/HCV coinfection ranges from 12% to 28% with mother-to-child transmission rates ranging from 3.6% to 9.5%. There are no guidelines detailing the most appropriate clinical management and treatment of coinfected children. We used a semi-structured questionnaire to investigate current European practices for the management and follow-up of HIV/HCV coinfected children among clinical centres contributing to the European Collaborative Study or the European Paediatric HCV Network. Clinicians from 16 out of 24 clinical centres responded and were caring for a total of 44 HIV/HCV coinfected children. We found that, although there was a high level of concordance regarding testing for HIV and/or HCV infection, monitoring practices in these European centres varied widely. Few clinicians stated they would administer HIV and HCV treatment concurrently. Limited experience in the clinical management of this group and the lack of an evidence base to guide policy may be a barrier to achieving optimal care and treatment.


Peritoneal dialysis for refractory heart failure: A single-center experience.
Heart failure (HF) is a disease associated with poor quality of life. Peritoneal dialysis (PD) can be an alternative in the treatment of these patients to overcome fluid overload. The objective of this study is to observe the effects of PD in refractory HF patients. We conducted an observational study including 10 patients with refractory congestive HF. PD started solely for fluid overload. Patients' baseline parameters were compared with follow-up parameters. Median age was 57.5 (44.8-64.3) years. Median left ventricular ejection fraction was 20% (18.8-31.3), and all patients had right ventricular dysfunction. Median estimated glomerular filtration rate was 51.2 (43.8-101.3) ml/min/1.73 m2 . Two patients (20%) died during the follow-up period. New York Heart Association (NYHA) functional class decreased significantly from a median of 4 to 2,1 and 1 in the 3rd, 6th, and 12th months, respectively (p ≤ 0.01 for all from baseline). Number and length of hospitalization decreased significantly after treatment (number from a median of 3 to 0, p = 0.013; days from 50.5 to 0, p = 0.028). PD significantly reduced NYHA functional class, number and days of hospitalization for HF. It could be a reasonable option in chronic treatment of patients with refractory HF.


IRX3 Promotes the Browning of White Adipocytes and Its Rare Variants are Associated with Human Obesity Risk.
IRX3 was recently reported as the effector of the FTO variants. We aimed to test IRX3's roles in the browning program and to evaluate the association between the genetic variants in IRX3 and human obesity. IRX3 expression was examined in beige adipocytes in human and mouse models, and further validated in induced beige adipocytes. The browning capacity of primary preadipocytes was assessed with IRX3 knockdown. Luciferase reporter analysis and ChIP assay were applied to investigate IRX3's effects on UCP1 transcriptional activity. Moreover, genetic analysis of IRX3 was performed in 861 young obese subjects and 916 controls. IRX3 expression was induced in the browning process and was positively correlated with the browning markers. IRX3 knockdown remarkably inhibited UCP1 expression in induced mouse and human beige adipocytes, and also repressed the uncoupled oxygen consumption rate. Further, IRX3 directly bound to UCP1 promoter and increased its transcriptional activity. Moreover, 17 rare heterozygous missense/frameshift IRX3 variants were identified, with a significant enrichment in obese subjects (P=0.038, OR=2.27; 95% CI, 1.02-5.05). IRX3 deficiency repressed the browning program of white adipocytes partially by regulating UCP1 transcriptional activity. Rare variants of IRX3 were associated with human obesity.


Devo-Aging: Intersections Between Development and Aging.
There are two fundamental questions in developmental biology. How does a single fertilized cell give rise to a whole body? and how does this body later produce progeny? Synchronization of these embryonic and postembryonic developments ensures continuity of life from one generation to the next. An enormous amount of work has been done to unravel the molecular mechanisms behind these processes, but more recently, modern developmental biology has been expanded to study development in wider contexts, including regeneration, environment, disease, and even aging. However, we have just started to understand how the mechanisms that govern development also regulate aging. This review discusses examples of signaling pathways involved in development to elucidate how their regulation influences healthspan and lifespan. Therefore, a better knowledge of developmental signaling pathways stresses the possibility of using them as innovative biomarkers and targets for aging and age-related diseases.


Mucormycosis: A Case Series.
Mucormycosis is a potentially life-threatening invasive fungal infection caused by diverse fungal organisms in the order Mucorales. Traditional risk factors of mucormycosis include poorly controlled diabetes, hematological malignancies such as leukemia and lymphoma, and post-transplant patients, with rhino-orbito-cerebral and pulmonary mucormycosis as common manifestations. We report four cases of mucormycosis precipitated by classical as well as atypical risk factors, with common sites of infection such as pulmonary and rhino-orbital to rare manifestations such as peritoneal mucormycosis. Diagnoses were confirmed by either a histopathological sample or a positive culture. Only one patient had concomitant positive culture and histopathology results. Low culture positivity rate has delayed the diagnosis of two cases. First-line antifungal therapy was limited to amphotericin B deoxycholate in three cases due to financial cost, but all patients responded to the treatment. There were two mortalities, but both were unrelated to disease progression. All cases had source control done, except for the patient with pulmonary mucormycosis, due to poor lung reserve which refrained him from surgery. With emerging evidence of local therapies for endobronchial lesions, they potentially serve as an alternative for patients who are not suitable for operation. This case series also aims to contribute to the local epidemiology of mucormycosis, highlights the importance of early diagnosis, and draws attention from stakeholders to the challenges faced in managing this life-threatening infection.


The ecological validity of neuropsychological tests: a review of the literature on everyday cognitive skills.
Evaluating the ecological validity of neuropsychological tests has become an increasingly important topic over the past decade. In this paper, we provide a comprehensive review of the research on the ecological validity of neuropsychological tests, as it pertains to everyday cognitive skills. This review is presented in the context of several theoretical issues facing ecological validity research. Overall, the research suggests that many neuropsychological tests have a moderate level of ecological validity when predicting everyday cognitive functioning. The strongest relationships were noted when the outcome measure corresponded to the cognitive domain assessed by the neuropsychological tests. Several other factors that may moderate the degree of ecological validity established for neuropsychological tests are in need of further exploration. These factors include the effects of the population being tested, the approach utilized (verisimilitude vs. veridicality), the person completing the outcome measure (significant other vs. clinician), illness severity, and time from injury until evaluation. In addition, a standard measurement of outcome for each cognitive domain is greatly needed to allow for comparison across studies.


Efficacy and safety of CT-guided percutaneous thermal ablation for hepatocellular carcinoma adjacent to the second porta hepatis.
Purpose: This study assessed the efficacy and safety of computed tomography (CT)-guided percutaneous thermal ablation for hepatocellular carcinoma adjacent to the second porta hepatis.Methods: From January 2011 to June 2018, 59 consecutive patients (51 men and 8 women aged 29-85 years) with 65 tumors (mean maximum tumor diameter: 20.5 ± 1.2 mm; range: 5-50 cm) adjacent to the second porta hepatis underwent percutaneous CT-guided thermal ablation. The complete ablation rate, local progression-free survival (LPFS), progression-free survival (PFS), prognostic factors for local progression, and safety of this technique were assessed.Results: No more than three sessions were performed to complete a patient's treatment. Technical success was achieved for all tumors. In the median follow-up of 18.5 months, local tumor progression occurred in 32.2% (19/59) of patients, while tumor progression occurred in 71.2% (42/59). The median LPFS was 37.4 months. The 1-, 2-, and 3-year LPFS rates were 86.2%, 66.5%, and 66.5%, respectively. The median PFS was 11.0 months. The 1-, 2-, and 3-year PFS rates were 47.9%, 27.0%, and 20.2%, respectively. The tumor size (P = .007) and distance between the tumor and inferior vena cava (P = 0.018) were the independent prognostic factors for local tumor progression.Conclusion: We showed that CT-guided percutaneous microwave ablation and radiofrequency ablation are effective and safe treatments for tumors adjacent to the second porta hepatis, particularly in patients with lesions less than 3 cm and a distance between the tumor and inferior vena cava of more than 5 mm.


Atypical Hybrid Metal-Organic Frameworks (MOFs): A Combinative Process for MOF-on-MOF Growth, Etching, and Structure Transformation.
The structural, compositional, and morphological features of metal-organic frameworks (MOFs) govern their properties and applications. Construction of hybrid MOFs with complicated structures, components, or morphologies is significant for the development of well-organized MOFs. An advanced route is reported for construction of atypical hybrid MOFs with unique morphologies and complicated components: 1) MOF-on-MOF growth of a 3D zeolitic imidazolate framework (ZIF) on a ZIF-L template, 2) etching of a part of the 2D ZIF-L template, and 3) structural transformation of 2D ZIF-L into 3D ZIF. The formation of core-shell-type MOF rings and plates is controlled by regulating the three processes. The formation route for the core-shell-type MOF rings and plates was monitored by tracking changes in morphology, structure, and composition. Carbon materials prepared from the pyrolysis of the core-shell-type hybrid MOFs displayed enhanced oxygen reduction reaction activities compared to their monomeric counterparts.


Thermal effect on corneal incisions with different phacoemulsification ultrasonic tips.
To evaluate the thermal effects of 3 phacoemulsification ultrasound (US) tips (standard, MicroTip, and Mackool) on the corneal incision based on the tip's position. Department of Ophthalmology, Tokyo Dental College, Tokyo, Japan. Thermal changes were recorded with an infrared thermal video during phacoemulsification in 18 porcine eyes. The 3 US tips were placed in 3 positions (primary, roofing, and flanking) in the corneal incision, and the resultant temperature changes were recorded. With the 3 US tips in the primary position, the temperature remained under 36 degrees C. When the tips were in the roofing position, a marked temperature increase (51.4 degrees C) was observed with the standard tip; with the MicroTip, a temperature increase occurred but was lower than with the standard tip; with the Mackool tip, the temperature remained stable. The temperature around the incision site increased with all tips when they were moved toward the corner of the incision, which resulted in direct contact with the silicone sleeve. This change was most obvious with the standard tip (temperature 51.5 degrees C), and a wound burn was observed. With the MicroTip, the temperature increase was moderate (44.2 degrees C), and the wound burn area was smaller. With the Mackool tip, the temperature increased the least (42.1 degrees C). The position of the US tips resulted in a temperature increase in the incision area and caused wound burn. Newly developed US tips could minimize this complication.


H-2 antigens of certain t and non-t mice react with the same monoclonal antibody.
Monoclonal antibody 212.i.4.2 mediated complement-dependent lysis of spleen and lymph node cells carrying the tw1 , tw12 , tw71 , t6, tw73 , and tLub1 haplotypes, while cells from mice carrying 11 other t haplotypes were not lysed. The antibody also detected an epitope controlled by genes in the H-2Dd region of non-t mice. A molecule of 46,000 molecular weight was immunoprecipitated by 212.i.4.2 from detergent extracts of 125I-labelled spleen cells of +/ tw12 and B10.D2 mice. The H- 2dm2 mutation did not alter the expression of the epitope recognized by 212.i.4.2. However, the H- 2dm1 mutation decreased the reactivity of lymphoid cells with the antibody in cytotoxicity tests, and 212.i.4.2 immunoprecipitated little or no protein from extracts of B10.D2( R106 ) spleen cells which carry the H- 2dm1 mutation.


Safety and feasibility of robotic percutaneous coronary intervention: PRECISE (Percutaneous Robotically-Enhanced Coronary Intervention) Study.
The aim of this study was to evaluate the safety as well as the clinical and technical effectiveness of robotic-assisted percutaneous coronary intervention. Robotic systems have been suggested to enhance the performance of cardiovascular procedures, as well as to provide protection from the occupational hazards that are associated with interventional practice. Patients with coronary artery disease and clinical indications for percutaneous intervention were enrolled. The coronary intervention was performed with the CorPath 200 robotic system, which consists of a remote interventional cockpit and a bedside disposable cassette that enables the operator to advance, retract, and rotate guidewires and catheters. The primary endpoints were clinical procedural success, defined as <30% residual stenosis at the completion of the robotic-assisted procedure without major adverse cardiovascular events within 30 days, and device technical success, defined as the successful manipulation of the intracoronary devices using the robotic system only. A total of 164 patients were enrolled at 9 sites. Percutaneous coronary intervention was completed successfully without conversion to manual operation, and device technical success was achieved in 162 of 164 patients (98.8%). There were no device-related complications. Clinical procedural success was achieved in 160 of 164 patients (97.6%), whereas 4 (2.4%) had periprocedural non-Q-wave myocardial infarctions. No deaths, strokes, Q-wave myocardial infarctions, or revascularization occurred in the 30 days after the procedures. Radiation exposure for the primary operator was 95.2% lower than the levels found at the traditional table position. This pivotal multicenter study with a robotic-enhanced coronary intervention system demonstrated the safety and feasibility of the system. The robotic remote-control procedure met the expected technical and clinical performance, with significantly lower radiation exposure to the operator. (Evaluation of the Safety and Effectiveness of the CorPath 200 System in Percutaneous Coronary Interventions [PCI] [PRECISE]; NCT01275092).


A computational model of cerebellar cortex and peripheral muscle.
A computational model, suitable for analytical or machine simulation studies, is developed for a specific cerebellar loop, the pathway from muscle fibre stretch receptors to the cerebellar cortex and back again. The model adheres to physiological data from the cat, and employs features from several existing models, including a single neuron model developed and tested earlier. Also included is a mechanical equivalent to an idealised muscle, in this case a rectangular array of muscle fibres which map 1-to-1 onto the array of compartments which form the cerebellar cortex. Much of the literature on cerebellar models is briefly reviewed, as are several key physiological experiments.


Role of lymphoscintigraphy for selective sentinel lymphadenectomy.
An essential prerequisite for a successful sentinel node biopsy (SNB) procedure is an accurate map of the pattern of lymphatic drainage from the primary tumor site. The role of lymphoscintigraphy (LS) in SNB is to provide such a map in each patient. This map should indicate not only the location of all sentinel nodes but also the number of SNs at each location. Such mapping can be achieved using 99mTc-labeled small particle radiocolloids, high-resolution collimators with minimal septal penetration, and imaging protocols that detect all SNs in every patient regardless of their location. This is especially important in melanoma patients, since high-quality LS can identify the actual lymphatic collecting vessels as they drain into each SN. The SN is not always found in the nearest node field and is best defined as "any lymph node receiving direct lymphatic drainage from a primary tumor site." Reliable clinical prediction of lymphatic drainage from the skin or breast is not possible. Patterns of lymphatic drainage from the skin are highly variable from patient to patient, even from the same area of the skin. Unexpected lymphatic drainage has been found from the skin of the back to SNs in the triangular intermuscular space and in some patients through the posterior body wall to SNs in the para-aortic, paravertebral, and retroperitoneal areas. Lymphatic drainage from the head and neck frequently involves SNs in multiple node fields, and can occur from the base of the neck up to nodes in the occipital or upper cervical areas or from the scalp down to nodes at the neck base, bypassing many other node groups. Lymphatic drainage from the upper limb can be directly to SNs above the axilla. Drainage to the epitrochlear region from the hand and arm is more common than was previously thought as is drainage to the popliteal region from the foot and leg. Interval nodes, which lie along the course of a lymphatic vessel between a melanoma site and a recognised node field, are not uncommon especially on the trunk. Drainage across the midline of the body is quite frequent on the trunk and in the head and neck region. In breast cancer, although dynamic imaging is usually not possible, an early postmassage image will also often visualize the lymphatic vessels leading to the SN allowing them to be differentiated from any second tier nodes. Small radiocolloid particles are also needed to achieve migration from peritumoral injections sites and LS allows accurately detection of SNs outside the axilla, which occur in about 50% of patients. These nodes may lie in the internal mammary chain, the supraclavicular region, or the interpectoral region. Intramammary interval nodes can also be SNs in some patients. The location of the cancer in the breast is not a reliable guide to lymphatic drainage, since lymph flow often crosses the center line of the breast. Micrometastatic disease can be present in any SN regardless of its location, and for the SNB technique to be accurate all true SNs must be identified and removed in every patient. LS is an important first step in ensuring that this goal is achieved.


Zonisamide in pediatric epilepsy: review of the Japanese experience.
Zonisamide is a novel anticonvulsant that is structurally and mechanistically unique, compared with other antiepilepsy drugs. Available in Japan and South Korea since 1989, it was approved in the United States in the year 2000 as adjunctive therapy for partial seizures in adults. There has been extensive clinical trial and clinical practice experience with zonisamide therapy in Japanese children. Open-label data from pediatric clinical trials conducted in Japan suggest that zonisamide is well tolerated and effective against partial- and generalized-onset seizures in children. Despite this wealth of open-label data, no formal pharmacokinetic studies and only one well-controlled trial of zonisamide's efficacy and safety in Japanese children have been completed to date. No controlled clinical trials of zonisamide in children have been completed in the United States or Europe. Additional controlled trials in children with partial- or generalized-onset seizures, infantile spasms, and Lennox-Gastaut syndrome are warranted to further delineate zonisamide's broad spectrum of efficacy and tolerability in children.


Primary paediatric epidural sarcomas: molecular exploration of three cases.
Primary paediatric epidural sarcomas are extremely rare. Overall, there remains a paucity of knowledge in paediatric epidural sarcomas owing to the infrequent number of cases. The Archer FusionPlex Sarcoma Kit (ArcherDX, Inc) is a next-generation sequencing assay that has been reported to be a useful technique to detect recurrent fusion in sarcomas. We report the molecular exploration of 3 primary paediatric epidural sarcomas-one in the cranium (mesenchymal chondrosarcoma) and 2 in the spine (mesenchymal chondrosarcoma and Ewing sarcoma respectively). This is a study approved by the hospital ethics board. Clinico-pathological information from 3 consenting patients with primary epidural sarcomas was collected. These selected tumours are interrogated via Archer FusionPlex Sarcoma Kit (ArcherDX, Inc) for genomic aberrations. Results were validated with RT-PCR and Sanger sequencing. All findings are corroborated and discussed in concordance with current literature. Our findings show 2 variants of the HEY1-NCOA2 gene fusion: HEY1 (exon 4)-NCOA2 (exon 13) and HEY1 (exon 4)-NCOA2 (exon 14), in both mesenchymal chondrosarcoma patients. Next, the Ewing sarcoma tumour is found to have EWSR1 (exon 10)-FLI1 (exon 8) translocation based on NGS. This result is not detected via conventional fluorescence in situ testing. This is a molecularly-centered study based on 3 unique primary paediatric epidural sarcomas. Our findings to add to the growing body of literature for these exceptionally rare and malignant neoplasms. The authors advocate global collaborative efforts and in-depth studies for targeted therapy to benefit affected children.


Predictors of hospital readmission after discharge in patients with congestive heart failure.
The purposes of this study were to (1) describe the characteristics of the population with congestive heart failure (CHF) who were admitted to a large, southeastern, acute-care hospital and (2) determine which patients are at risk for readmissions within 6 months. A descriptive correlational design, using variables maintained in a computerized data bank on patients with CHF (N = 557, 39% were black) who were admitted between October 2000 and March 2002, was used to describe the adult population with CHF and identify variables associated with a likelihood of readmission. In the 6 months after the index admission, 224 (40%) of the patients were readmitted to the hospital for CHF. Variables significantly associated with readmission included lack of cardiology consult during admission, living status, point of entry of index admission, receiving Medicare, and having pulmonary hypertension. Four models, composed of subsets of variable from the data bank were developed and tested with logistic regression. The model composed of discharge variables was the only model that predicted readmission at a significant level. There is a need to develop comprehensive data banks to describe patterns of care and their outcomes. Such data should inform plans to manage this vulnerable population.


Otosclerosis and sensorineural hearing loss: a histopathologic study.
The precise role and mechanism whereby otosclerosis is associated with sensorineural hearing loss remains unclear. Previous histopathologic reports are inconsistent with regard to the location of the otosclerotic focus, invasion of the otic capsule, and the number of remaining peripheral sensorineural elements. From the combined temporal bone collections of the University of Chicago and the Mayo Clinic, we identified a group of 125 ears from 80 patients, all with confirmed otosclerosis. Six of these ears were associated clinically with sensorineural hearing loss without stapes fixation. The histopathology of the otosclerotic focus was reviewed in terms of its location and depth of invasion. The cochlea and spiral ganglion were reconstructed, and the state of the organ of Corti and the presence or absence of peripheral cochlear nerve fibers were noted. Correlations with ganglion cell counts were made. The present study showed that the pattern of degeneration of peripheral sensory and neural elements in the cases presented is very similar to that found in cases of age-related processes such as presbycusis.


Increasing blood oxygen increases an index of 5-HT synthesis in human brain as measured using alpha-[(11)C]methyl-L-tryptophan and positron emission tomography.
The main objective of this investigation was to test the hypothesis that brain serotonin (5-HT) synthesis, as measured by trapping of alpha-[(11)C]methyl-L-tryptophan (alpha-MTrp) using positron emission tomography (PET), can be modulated by changes in blood oxygen. The study involved six healthy participants (three male and three female), who breathed a 15% or 60% oxygen mixture starting 15 min before the injection of tracer and continuing during the entire acquisition period. Participants were injected with up to 12m Ci of alpha-MTrp. Two sets of PET images were acquired while the participants were breathing each of the oxygen mixtures and, after reconstruction, all images were converted into brain functional images illustrating the brain trapping constant K(*) (microL/g/min). The K(*) values were obtained for 12 regions of interest outlined on the magnetic resonance images. The K(*) values obtained at high and low blood oxygen content were compared by paired statistics using Tukey's post hoc correction. As there were no difference in plasma tryptophan concentrations, these K(*) values are directly related to regional 5-HT synthesis. The results showed highly significant increases (50% on average) in brain serotonin synthesis (K(*) values) at high (mean value of 223+/-41 mmHg) relative to low (mean value 77.1+/-7.7 mmHg) blood oxygen levels. This suggests that tryptophan hydroxylase is not saturated with oxygen in the living human brain and that increases in blood oxygen can elevate brain serotonin synthesis.


Effects of eslicarbazepine as add-on therapy on sleep architecture in temporal lobe epilepsy: results from "Esleep" study.
Studies looking at the effect of antiseizure medications (ASMs) on the sleep microstructure of subjects with epilepsy are scarce. This study aims to evaluate the impact of eslicarbazepine (ESL) as add-on therapy on the sleep microstructure in temporal lobe epilepsy (TLE). Twelve patients affected by TLE were recruited to undergo overnight polysomnography and a subjective evaluation of nocturnal sleep utilizing the Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence through the Epworth Sleepiness Scale (ESS) before and after three months of treatment with ESL as add-on therapy. Ten healthy controls (HC) matched for age, sex and BMI were recruited. Scoring and analysis of sleep macrostructure and cyclic alternating pattern (CAP) parameters were performed. Ten patients completed the study. The comparison between patients in basal condition (T0) and HC showed a significant lower sleep efficiency (p = 0.049), REM percentage (p = 0.002), higher REM latency (p = 0.02), N2 (p = 0.001) and WASO (p = 0.01). Regarding CAP, patients at T0 showed higher CAP rate in N1 (p = 0.01), lower A1 (%) (p = 0.03), higher A3 (%) (p = 0.01), higher mean duration of A (p = 0.02) and A3 (p = 0.006), A3 index (p = 0.02) than HC. ESL did not induce any significant changes in nocturnal macrostructural polysomnographic variables and PSQI scores. Furthermore, the ESS score showed no modification after treatment. Lower CAP rate in N3 (p = 0.02), phase A2 index (p = 0.02) average number of CAP cycle per sequences and mean duration of CAP sequences (both p = 0.02) was evident after ESL. A trend toward significance was evident for the decrease of CAP rate in N1 (p = 0.09) and N2 (p = 0.09), and for the increase of B phase mean duration (p = 0.07). We found significant improvement in sleep continuity as measured by CAP after ESL. These findings suggest that ESL may positively modulate sleep fragmentation in patients with TLE, and hence enhance sleep quality. Our results suggest a favourable sleep profile with the use of ESL.


Assaying Mitochondrial Function by Multiparametric Flow Cytometry.
Flow cytometry has been a vital tool in cell biology for decades based on its versatile ability to detect and quantifiably measure both physical and chemical attributes of individual cells within a larger population. More recently, advances in flow cytometry have enabled nanoparticle detection. This is particularly applicable to mitochondria, which, as intracellular organelles have distinct subpopulations that can be evaluated based on differences in functional, physical, and chemical attributes, in a manner analogous to cells. This includes distinctions based on size, mitochondrial membrane potential (ΔΨm), chemical properties, and protein expression on the outer mitochondrial membrane in intact, functional organelles and internally in fixed samples. This method allows for multiparametric analysis of subpopulations of mitochondria, as well as collection for downstream analysis down to the level of a single organelle. The present protocol describes a framework for analysis and sorting mitochondria by flow cytometry, termed fluorescence activated mitochondrial sorting (FAMS), based on the separation of individual mitochondria belonging to subpopulations of interest using fluorescent dyes and antibody labeling.


Increasing the damping of oscillatory systems with an arbitrary number of time varying frequencies using fractional-order collocated feedback.
This paper studies the active damping of the oscillations of lightly damped linear systems whose parameters are indeterminate or may change through time. Systems with an arbitrary number of vibration modes are considered. Systems described by partial differential equations, that yield an infinite number of vibration modes, can also be included. In the case of collocated feedback, i.e. the sensor is placed at the same location of the actuator, a simple fractional order differentiation or integration of the measured signal is proposed that provides an effective control: (1) it guarantees a minimum phase margin or damping of the closed-loop system at all vibration modes, (2) this feature is robustly achieved, i.e., it is attained for very large variations or uncertainties of the oscillation frequencies of the system and (3) it is robust to spillover effects, i.e., to the unstabilizing effects of the vibration modes neglected in the controller design (especially important in infinite dimensional systems). Moreover, the sensitivity of the gain crossover frequency to such variations is assessed. Finally, these results are applied to the position control of a single link flexible robot. Simulated results are provided.


A novel vitivirus-like sequence found in Arracacia xanthorrhiza plants by high throughput sequencing.
High throughput sequencing (HTS) is a very powerful tool for detecting and discovering novel viral-like sequences without prior knowledge of the sequence. Here we describe the complete genome of a new vitivirus-like sequence that was found in arracacha (Arracacia xanthorrhiza) plants using HTS technology. The complete genome sequence was validated by Sanger sequencing. The genomic organization of the new putative vitivirus resembles that of grapevine virus B (GVB) and grapevine virus D (GVD). The putative coat protein showed 41 to 49% identity with similar proteins of known vitiviruses, while the RNA-dependent RNA polymerase shared 52 to 55% identity with those encoded by grapevine vitiviruses. Based on the demarcation criteria for the genus Vitivirus, the virus described in this work, provisionally named as "Arracacha virus V", represents a novel species in this taxon.


Contamination by polychlorinated biphenyls (PCBs) in striped dolphins (Stenella coeruleoalba) from the Southeastern Mediterranean Sea.
Concentrations of polychlorinated biphenyls (PCBs) including dioxin-like PCBs (non-ortho, PCB 77, PCB 126, and PCB 169 and mono-ortho, PCB 105, PCB 118, and PCB 156) were measured in different organs and tissues (melon, blubber, liver, kidney, lung, heart, and muscle tissue) of striped dolphins (Stenella coeruleoalba) from the Eastern Mediterranean Sea (Adriatic Sea). The mean highest levels were in blubber and melon, followed by liver, kidney, lung, heart, and muscle tissue. PCB profiles were similar in all tissues and organs being dominated by the higher chlorinated homologues (hexa-CBs, 55.8-62.1%; penta-CBs, 15.4-20.0%; and hepta-CB PCB 180, 12.7-16.5%). Major PCBs in all tissues were congeners 138 and 153 collectively accounting for 50.6-58.3% of the total PCB concentrations, followed by PCB 101, 105, 118, and 180 constituting from 27.0% to 31.0%. PCB levels were higher in adult males than in adult females. The estimated 2,3,7,8-TCDD toxic equivalents of non- and mono-ortho PCBs were much higher than the threshold level above which adverse effects have been observed in other marine mammals species, suggesting that striped dolphins in this region are at risk for toxic effects.


Growth inhibition of cartilaginous embryonic chick tibiae by ionizing radiation: an in vitro study.
The radiation effect on the longitudinal growth of cartilaginous tibiae of 6,5 day old chick embryos is studied in vitro. After irradiation length is measured daily during the 3 days culture period and incorporation of (3)H-thymidine, (3)H-uridine or (3)H-proline is sampled by liquid scintillation counting. Selective tibiae are videorecorded during the incubation period. Morphology is studied by light microscopy, autoradiography and electron microscopy.Growth inhibition is only restricted to 5% at 20 Gy up to 20% at 150 Gy. The (3)H-uridine and (3)H-proline incorporation is only decreased by 21 and 32% at 150 Gy. (3)H-thymidine incorporation on the contrary shows 17% decrease at 2 Gy. Irradiation at 200 Gy gives a total growth arrest and stops incorporation of all used labeled compounds in 75% of the specimens. L.M. and E.M. show no morphological differences between irradiated and sham irradiated tibiae until 150 Gy. At 200 Gy however necrosis of the cells is observed.We conclude that longitudinal growth of cartilaginous tibiae in organ culture is not correlated with DNA synthesis but with cell hypertrophy and production of extracellular material. RNA transcription and synthesis of collagen fibers are radioresistant processes. This explains the limited influence of irradiation on the longitudinal growth.


Genomic evidence for the retention of the essential mycobacterial cell wall in the otherwise defective Mycobacterium leprae.
The obligate intracellularism of Mycobacterium leprae may be attributable to the effects of mutations in major metabolic areas due to a genome capable of encoding only about 1600 proteins. Yet cell wall biosynthesis capability remains relatively intact and comparisons with the genome of Mycobacterium tuberculosis provide insights into the genetic basis of a minimal mycobacterial cell wall.


Implementation of novel and conventional outbreak control measures in managing COVID-19 outbreaks in a large UK prison.
Outbreak control measures during COVID-19 outbreaks in a large UK prison consisted of standard (e.g., self-isolation) and novel measures, including establishment of: (i) reverse cohorting units for accommodating new prison admissions; (ii) protective isolation unit for isolating symptomatic prisoners, and (iii) a shielding unit to protect medically vulnerable prisoners. Single-centre prospective longitudinal study (outbreak control study), implementing novel and traditional outbreak control measures to prevent a SARS-COV-2 outbreak. The prison held 977 prisoners and employed 910 staff at that start of the outbreak. 120 probable and 25 confirmed cases among prisoners and staff were recorded between March and June 2020 during the first outbreak. Over 50% of initial cases among prisoners were on the two wings associated with the index case. During the second outbreak, 182 confirmed cases were recorded after probable reintroduction from a staff member. Widespread testing identified 145 asymptomatic prisoners, 16.9% of the total prisoner cases. The cohorting units prevented re-infection from new prison admissions and the shielding unit had no COVID-19 infections linked to either outbreak. Identifying and isolating infected prisoners, cohorting new admissions and shielding vulnerable individuals helped prevent uncontrollable spread of SARS-COV-2. These novel and cost-effective approaches can be implemented in correctional facilities globally.


Resveratrol improves motor function in patients with muscular dystrophies: an open-label, single-arm, phase IIa study.
Muscular dystrophies (MDs) are inherited disorders characterized by progressive muscle weakness. Previously, we have shown that resveratrol (3,5,4'-trihydroxy-trans-stilbene), an antioxidant and an activator of the protein deacetylase SIRT1, decreases muscular and cardiac oxidative damage and improves pathophysiological conditions in animal MD models. To determine whether resveratrol provides therapeutic benefits to patients with MDs, an open-label, single-arm, phase IIa trial of resveratrol was conducted in 11 patients with Duchenne, Becker or Fukuyama MD. The daily dose of resveratrol was 500 mg/day, which was increased every 8 weeks to 1000 and then 1500 mg/day. Primary outcomes were motor function, evaluated by a motor function measure (MFM) scale, muscular strength, monitored with quantitative muscle testing (QMT), and serum creatine kinase (CK) levels. Adverse effects and tolerability were evaluated as secondary outcomes. Despite the advanced medical conditions of the patients, the mean MFM scores increased significantly from 34.6 to 38.4 after 24 weeks of medication. A twofold increase was found in the mean QMT scores of scapula elevation and shoulder abduction. Mean CK levels decreased considerably by 34%. Diarrhoea and abdominal pain was noted in six and three patients, respectively. Resveratrol may provide some benefit to MD patients.


Osteonecrosis of the jaw in an AIDS patient: a case report.
We report a rare case of osteonecrosis of the jaw following necrotizing gingivitis in a Japanese AIDS patient. Intraoral examination showed exposed necrotic bone in the left mandible and spontaneous loss of teeth. This patient was successfully treated with highly active anti-retroviral therapy combined with minimally invasive surgical procedures to remove the osteonecrosis of the jaw.


Research progress on the pathogenesis of CDKL5 pathogenic variants and related encephalopathy.
Cyclin-dependent kinase-like 5 (CDKL5) is a gene encoding a serine/threonine kinase that possesses an N-terminal catalytic domain and a large C-terminal domain and is located on the short arm of the X-chromosome at position 22 (Xp22). CDKL5 regulates neuronal migration, axonal growth, dendritic morphogenesis, and synaptic development and affects synaptic function. Pathogenic variants include deletions, truncations, splice variants, and missense variants. The specificity of CDKL5 is mainly determined by the shared sequence of amino acid residues, which is the phosphorylation site of the target protein with the motif Arg-Pro-X-Ser/Thr-Ala/Pro/Gly/Ser (R-P-X-[S/T]-[A/G/P/S]). Developmental encephalopathy caused by pathogenic variants of CDKL5 has a variety of nervous system symptoms, such as epilepsy, hypotonia, growth retardation, dyskinesia, cortical visual impairment, sleep disorders, and other clinical symptoms. This review summarizes the mechanism of CDKL5-induced allogeneic lesions in the nervous system and the clinical manifestations of related encephalopathy. Conclusion: This review clarifies CDKL5's participation in neurodevelopmental diseases as well as its crucial function in dividing cells, cultured neurons, knockout mice, and human iPSC-derived neurons. CDKL5 variants help identify clinical diagnostic biomarkers. Although a few direct substrates of CDKL5 have been identified, more must be found in order to fully comprehend the signaling pathways connected to CDKL5 in the brain and the mechanisms that underlie its activities.


Assessment of violence against women in Kano metropolis, Nigeria.
Violence against women, in its various forms, is endemic in communities and countries around the world, cutting across class, education, race, age, religious and national boundaries. This descriptive cross-sectional study was conducted to identify various forms of gender based violence affecting women in Kano metropolis, determine factors responsible for gender based violence and use this to suggest ways of preventing gender based violence. Respondents for this study were selected from the eight metropolitan Local Government Areas of Kano State, Nigeria. Six hundred adult males and females were selected through a multi-stage sampling technique by the use of questionnaire as the data tool. More than three quarters 436 (75.7%) of the respondents knew that women are subjected to various forms of verbal abuse in their homes by their spouses. Deprivation of assess to health care and education was identified by 454 (78.8%) and 490 (85.15) respondents as challenges faced by women at homes. Majority of the respondents 498 (86.4%) identified financial reason, four hundred and forty (76.4%) respondents mentioned unfaithfulness and three-quarters 434 (75.3%) of the respondents said refusal of sexual advance is a reason for violence activities witnessed by women in their respective homes. There was a statistically significant relationship in opinion of male and female on coercion of wife for sexual activities when she is tired and when she is not in the mood (p-value=0.0000). Government and Non Governmental organisation should intensify activities to promote awareness and advocacy on violence against women. Involvement of males in all programmes relating to violence against women should be done especially since the perpetrators in most cases are men.


Defining functional signatures of dysbiosis in periodontitis progression.
Periodontitis is a common inflammatory disease that leads to tooth loss and has been linked to cardiovascular disease and diabetes mellitus. The periodontal microbiome is highly diverse, and metatranscriptomic studies have indicated that the genes that are expressed by the microbiota are more relevant than the microbial composition in the pathogenesis of periodontitis. A recent study of early metabolic activities in the dysbiotic microbiome reveals a functional signature that distinguishes periodontal sites that will become inflamed, supporting the idea that microbial communities as a whole drive disease progression.


Neuro-genetic non-invasive temperature estimation: intensity and spatial prediction.
The existence of proper non-invasive temperature estimators is an essential aspect when thermal therapy applications are envisaged. These estimators must be good predictors to enable temperature estimation at different operational situations, providing better control of the therapeutic instrumentation. In this work, radial basis functions artificial neural networks were constructed to access temperature evolution on an ultrasound insonated medium. The employed models were radial basis functions neural networks with external dynamics induced by their inputs. Both the most suited set of model inputs and number of neurons in the network were found using the multi-objective genetic algorithm. The neural models were validated in two situations: the operating ones, as used in the construction of the network; and in 11 unseen situations. The new data addressed two new spatial locations and a new intensity level, assessing the intensity and space prediction capacity of the proposed model. Good performance was obtained during the validation process both in terms of the spatial points considered and whenever the new intensity level was within the range of applied intensities. A maximum absolute error of 0.5 degrees C+/-10% (0.5 degrees C is the gold-standard threshold in hyperthermia/diathermia) was attained with low computationally complex models. The results confirm that the proposed neuro-genetic approach enables foreseeing temperature propagation, in connection to intensity and space parameters, thus enabling the assessment of different operating situations with proper temperature resolution.


Antitumor Trans Platinum DNA Adducts: NMR and HPLC Study of the Interaction Between a trans-Pt Iminoether Complex and the Deoxy Decamer d(CCTCGCTCTC).d(GAGAGCGAGG).
The single-stranded oligonucleotide 5'-d(CCTCGCTCTC) (I) was reacted with the antitumor trans platinum iminoderivative trans-[PtCl(2){E-HN = C(OMe)Me}(2)] (trans-EE) and subsequently annealed with its complementary strand 5'-d(GAGAGCGAGG) (II). The platinated duplex was characterized by 1D and 2D proton NMR spectroscopy at 600 MHz. In agreement with previous studies by different techniques trans-EE was found to form a monofunctional adduct with the duplex involving the guanine residue. The modification by trans-EE has been found to induce only minor local distortion in the duplex geometry. Two key crosspeaks observed in the NOESY map corresponding to a close contact between G5-H8 and the methoxy and the methyl group, respectively, enabled us to dock the trans-EE complex with the duplex by geometry optimization. The results support the idea that the antitumor activity of trans-EE is related to lesion of DNA fundamentally different from that of cisplatin. Unexpectedly, the NOESY spectra indicated that at the high NaCl concentration used (0.2 M) the duplex was found to undergo slow deplatination. This was subsequently proved by HPLC. In a separate experiment on platination of the single strand in a salt free environment the HPLC analysis showed that the monofunctional adduct was not deplatinated, however, after 24 hours, additidnal minor isomers were detected.


Assaying the probabilities of obtaining maternally inherited heteroplasmy as the basis for modeling OXPHOS diseases in animals.
Gross alterations in cell energy metabolism underlie manifestations of hereditary OXPHOS (oxidative phosphorylation) diseases, many of which depend on proportion of mutant mitochondrial DNA (mtDNA) in tissues. An animal model of OXPHOS disease with maternal inheritance of mitochondrial heteroplasmy might help understanding the peculiarities of abnormal mtDNA distribution and its effect on pre- and postnatal development. Previously we obtained mice that carry human mtDNA in some tissues. It co-existed with murine mtDNA (heteroplasmy) and was transmitted maternally to the progeny of animals developed from zygotes injected with human mitochondria. To analyze the probability of obtaining heteroplasmic mice we increased the number of experiments with early embryos and obtained more specimens from F1. About 33% of zygotes injected with human mtDNA developed into post-implantation embryos (7th-13th days). Lower amount of such developed into neonate mice (ca. 21%). Among post-implantation embryos and in generations F0 and F1 percentages of human mtDNA-carriers were ca. 14-16%. Such percentages are sufficient for modeling maternally inherited heteroplasmy in small animal groups. More data are needed to understand the regularities of anomalous mtDNA distribution among cells and tissues and whether heart and muscles frequently carrying human mtDNA in our experiments are particularly susceptible to heteroplasmy.


Healthcare resource utilization and costs before and after long-acting injectable antipsychotic initiation in commercially insured young adults with schizophrenia.
Long-acting injectable (LAI) antipsychotics use is associated with improved adherence which can reduce the rate of relapse, hospitalization, and associated costs in patients with schizophrenia. Young adults could be at higher risk of poor adherence, hence use of LAI in this population may offer a benefit but the evidence is limited. This study aimed to compare clinical and economic outcomes before and after the initiation of LAI antipsychotics in commercially insured young adults (18-35 years of age) with schizophrenia. A retrospective claims data study was conducted using the data from the IBM MarketScan® Commercial Claims and Encounters (CCAE) Database. Patients with a continuous enrollment of at least 1-year before and 1-year after the first observed schizophrenia diagnosis (index date) and with the use of ≥1 typical or atypical LAI antipsychotic during the post-index follow-up period were included. A pre-post analysis was conducted to compare relapse rates, healthcare resource utilization, and costs before (from index date to LAI initiation) and after LAI initiation (to end of follow up). A total of 2222 patients who initiated LAIs after an index schizophrenia diagnosis were identified. The per patient per month (PPPM) composite relapse event rate (0.109 pre-LAI to 0.073 post-LAI) and hospitalization rate (0.091 to 0.058), all-cause inpatient visits (0.231 to 0.119), and length of stay (2.694 to 1.092 days) significantly decreased from before LAI initiation to after LAI initiation with similar trends seen for mental health and schizophrenia-related measures (all significant; P < 0.0001). All-cause total costs ($4898 to $3078 PPPM) were also decreased after LAI initiation, with similar trends seen for mental health and schizophrenia-related costs (all significant; P < 0.0001). Although medication costs were higher post-LAI period ($311 to $542 PPPM), the cost increase was substantially offset by the decreased costs associated with total healthcare costs. Treatment with LAI antipsychotics was associated with a decrease in relapse event rate, healthcare resource utilization, and costs after LAI initiation compared to before LAI initiation in commercially insured young adults with schizophrenia. Treatment with LAIs in young adults with schizophrenia is potentially associated with significant cost savings to commercial payers.


Tristetraprolin overexpression drives hematopoietic changes in young and middle-aged mice generating dominant mitigating effects on induced inflammation in murine models.
Tristetraprolin (TTP), encoded by Zfp36 in mice, is one of the best-characterized tandem zinc-finger mRNA binding proteins involved in mRNA deadenylation and decay. TTPΔARE mice lack an AU-rich motif in the 3'-untranslated regions of TTP mRNA, leading to increased TTP mRNA stability and more TTP protein, resulting in elevated mRNA decay rates of TTP targets. We examined the effect of TTP overexpression on the hematopoietic system in both young and middle-aged mice using TTPΔARE mice and found alterations in blood cell frequencies, with loss of platelets and B220 cells and gains of eosinophils and T cells. TTPΔARE mice also have skewed primitive populations in the bone marrow, with increases in myeloid-biased hematopoietic stem cells (HSCs) but decreases in granulocyte/macrophage-biased multipotent progenitors (MPP3) in both young and middle-aged mice. Changes in the primitive cells' frequencies were associated with transcriptional alterations in the TTP overexpression cells specific to age as well as cell type. Regardless of age, there was a consistent elevation of transcripts regulated by TNFα and TGFβ signaling pathways in both the stem and multipotent progenitor populations. HSCs with TTP overexpression had decreased reconstitution potential in murine transplants but generated hematopoietic environments that mitigated the inflammatory response to the collagen antibody-induced arthritis (CAIA) challenge, which models rheumatoid arthritis and other autoimmune disorders. This dampening of the inflammatory response was even present when there was only a small frequency of TTP overexpressing cells present in the middle-aged mice. We provide an analysis of the early hematopoietic compartments with elevated TTP expression in both young and middle-aged mice which inhibits the reconstitution potential of the HSCs but generates a hematopoietic system that provides dominant repression of induced inflammation.


Baricitinib: A Review in Severe Alopecia Areata.
Baricitinib (Olumiant®), a Janus kinase (JAK) inhibitor, is the first drug approved for the treatment of severe alopecia areata in the USA and the EU. Severe alopecia areata is usually difficult to treat and relapse is common. Patients with this disorder are more likely to suffer from anxiety and depression. In two pivotal placebo-controlled phase 3 clinical trials in adults with severe alopecia areata, oral baricitinib once daily was associated with clinically meaningful scalp, eyebrow, and eyelash hair regrowth over 36 weeks. Baricitinib was generally well tolerated with the most common adverse events being infections, headaches, acne, and elevated levels of creatine phosphokinase. While longer-term data will be necessary to more fully understand the benefits and risks of the drug, currently available data suggest that baricitinib is a useful treatment for patients with severe alopecia areata.


Nutrition, acid-base status and growth in early childhood.
Optimal growth is only possible in a well-balanced "inner milieu". Premature infants are especially vulnerable for disturbances of acid-base metabolism with a predisposition to metabolic acidosis due to a transient disproportion between age-related low renal capacity for net acid excretion (NAE) and an unphysiologically high actual renal NAE on nutrition with standard formulas. During a 50 month period, 452 low birth-weight infants were screened for spontaneous development of incipient late metabolic acidosis (ILMA), an early stage during the development of retention acidosis, characterized by maximum renal acid stimulation (MRAS, urine-pH < 5.4) on two consecutive days but still compensated systemic acid-base status. Compared with controls, patients with ILMA showed higher serum creatinine values, an increased urinary excretion of sodium, aldosterone and nitrogen, but only slightly lower blood pH (7.38 vs 7.41) and base excess (-2.8 vs. 0.2 mmol/l) with respiratory compensation (PCO2 35 vs 37 mm Hg). Patients with altogether 149 episodes of ILMA were subsequently randomly allocated to either treatment with NaHCO3 2 mmol/kg/d for 7 days or no special therapy in protocol I, or NaHCO3 vs NaCl each 2 mmol/kg/d for 7 days in protocol II. Patients of protocol I with persistent MRAS for 7 days showed lowest weight gain and a tendency for a further increase in urinary aldosterone and nitrogen excretion. NaCl supplementation (protocol II) seemed to promote weight gain without affecting either impaired mineralization or suboptimal nitrogen retention. Patients with alkali therapy under both protocols showed normal weight gain and normalization of hormonal stimulation, mineralization (protocol II) and nitrogen assimilation. Modification of the mineral content of a standard preterm formula decreased renal NAE to the low level seen on alimentation with human milk and reduced the incidence of ILMA in preterm and small-for-gestational-age infants to 1%. The data show that ILMA is associated with impaired growth. Activation of secondary homeostatic mechanisms (extracellular volume contraction, depletion of disposable net base pools) might be important for impaired growth. Production of new formulas for reduced renal NAE could be an effective general preventive measure to reduce the clinical importance of one component of mixed acid-base disorders in early childhood.


Tinnitus and Cognition: Linked?
Tinnitus is conscious auditory perception without corresponding external stimuli resulting from neuronal activity along auditory pathway either in peripheral or central auditory system. The exact origin, pathophysiologic pathway and its treatment is still under exploration. The main risk factor is hearing loss, but can occur in patients with normal hearing. Auditory brainstem response test helps to objectify this subjective complaint and aid in locating its origin. P300 is late latency auditory evoked potential, objective marker of cognitive potential. The purpose of our study was to ascertain any significant difference in P300 latency and amplitude values in cases of sensorineural hearing loss with tinnitus when compared to controls (normal hearing subjects) and also to find any correlation between severity of tinnitus and cognition. This was a case control study conducted at the department of ENT at Safdarjung Hospital, New Delhi between September 2016 to March 2018. The study comprised of one hundred and six patients, out of which fifty five patients were having sensorineural hearing loss with tinnitus and fifty one patients were normal hearing subjects. General medical and audiological history and examination was done. Significant increase in P300 latency and decrease in P300 amplitude was found in sensorineural hearing loss with tinnitus cases on comparing with controls. The similar pattern of P300 values was observed on increasing severity of tinnitus and degree of hearing loss. Hence, results revealed the role of cognition and involvement of central auditory pathway in tinnitus generation.


The roles of EZH2 in cancer and its inhibitors.
The enhancer of zeste homolog 2 (EZH2) is encoded by the Enhancer of zeste 2 polycomb repressive complex 2 subunit gene. EZH2 is involved in the cell cycle, DNA damage repair, cell differentiation, autophagy, apoptosis, and immunological modulation. The main function of EZH2 is to catalyze the methylation of H3 histone of H3K27Me3, which inhibits the transcription of target genes, such as tumor suppressor genes. EZH2 also forms complexes with transcriptions factors or directly binds to the promoters of target genes, leading to regulate gene transcriptions. EZH2 has been as a prominent target for cancer therapy and a growing number of potential targeting medicines have been developed. This review summarized the mechanisms that EZH2 regulates gene transcription and the interactions between EZH2 and important intracellular signaling molecules (Wnt, Notch, MEK, Akt) and as well the clinical applications of EZH2-targeted drugs.


Rare Complication of a Rare Malignancy: Case Report of Cardiac Amyloidosis Secondary to Waldenstrom Macroglobulinemia.
Cardiac amyloidosis is a rare disorder caused by the myocardial deposition of abnormal fibrils. A 52-year-old man was referred to our center with clinical features of heart failure, after cardiac magnetic resonance imaging showed restrictive cardiomyopathy. Abdominal fat pad biopsy showed features of amyloidosis, and after hematological workup, he was diagnosed with Waldenstrom macroglobulinemia (WM). He was initiated on a rituximab-based chemotherapy regimen, and his cardiac function was assessed serially. Because of non-response, he was switched to a bortezomib-based regimen. Unfortunately, three days into this regimen, the patient died. WM is a rare plasma cell dyscrasia with a nonspecific presentation. It uncommonly presents with sequelae of amyloidosis-the IgM subtype of amyloid-light chain (AL) amyloidosis. Diagnostic delays are common, contributing to an already poor prognosis. Amyloidosis in WM requires urgent treatment - clonal chemotherapy, and supportive cardiac care in heart involvement. Bortezomib-based regimens are commonly recommended, with diuretics as the mainstay for cardiac treatment. However, in most advanced cases, the prognosis is poor; thus, a high degree of suspicion is necessary for early diagnosis. This case illustrates the possible presentation of cardiac amyloidosis as a rare malignancy.


Function-structure connectivity in patients with severe brain injury as measured by MRI-DWI and FDG-PET.
A vast body of literature exists showing functional and structural dysfunction within the brains of patients with disorders of consciousness. However, the function (fluorodeoxyglucose FDG-PET metabolism)-structure (MRI-diffusion-weighted images; DWI) relationship and how it is affected in severely brain injured patients remains ill-defined. FDG-PET and MRI-DWI in 25 severely brain injured patients (19 Disorders of Consciousness of which 7 unresponsive wakefulness syndrome, 12 minimally conscious; 6 emergence from minimally conscious state) and 25 healthy control subjects were acquired here. Default mode network (DMN) function-structure connectivity was assessed by fractional anisotropy (FA) and metabolic standardized uptake value (SUV). As expected, a profound decline in regional metabolism and white matter integrity was found in patients as compared with healthy subjects. Furthermore, a function-structure relationship was present in brain-damaged patients between functional metabolism of inferior-parietal, precuneus, and frontal regions and structural integrity of the frontal-inferiorparietal, precuneus-inferiorparietal, thalamo-inferioparietal, and thalamofrontal tracts. When focusing on patients, a stronger relationship between structural integrity of thalamo-inferiorparietal tracts and thalamic metabolism in patients who have emerged from the minimally conscious state as compared with patients with disorders of consciousness was found. The latter finding was in line with the mesocircuit hypothesis for the emergence of consciousness. The findings showed a positive function-structure relationship within most regions of the DMN. Hum Brain Mapp 37:3707-3720, 2016. © 2016 Wiley Periodicals, Inc.


High-frequency oscillations mirror severity of human temporal lobe seizures.
Many patients with epilepsy have both focal and bilateral tonic-clonic seizures (BTCSs), but it is largely unclear why ictal activity spreads only sometimes. Previous work indicates that interictal high-frequency oscillations (HFOs), traditionally subdivided into ripples (80-250 Hz) and fast ripples (250-500 Hz), are a promising biomarker of epileptogenicity. We aimed to investigate whether HFOs correlate with the emergence of seizure activity and whether they differ between focal seizures (FSs) with impaired awareness and BTCSs. We retrospectively analyzed 15 FSs and 13 BTCSs from seven patients with mesial temporal lobe epilepsy, each of them with at least one BTCS and at least one FS. Representative intervals of intracranial electroencephalography from the seizure onset zone (SOZ) and remote non-SOZ areas were selected to compare pre-ictal, complex focal, tonic-clonic, and postictal periods. Ripples and fast ripples were visually identified and their density, that is, percentage of time occupied by the respective events, computed. Ripple and fast ripple densities increased inside the SOZ after seizure onset (P < 0.01) and in remote areas after progression to BTCSs (P < 0.01). Postictal SOZ ripple density dropped below pre-ictal levels (P < 0.001). Prior to onset of bilateral tonic-clonic movements, ripple density inside the SOZ is higher in BTCSs than in FSs (P < 0.05). Ripples and fast ripples correlate with onset and spread of ictal activity. Abundant ripples inside the SOZ may reflect the activation of specific neuronal networks related to imminent spread of seizure activity.


Optimization of haloacid dehalogenase production by recombinant E. coli BL21 (DE3)/pET-hakp1 containing haloacid dehalogenase gene from Klebsiella pneumoniae ITB1 using Response Surface Methodology (RSM).
Organohalogens, including monochloroacetic acid (MCA), are abundantly synthesized compounds for various industrial purposes. MCA is widely used as a raw material or as an intermediate compound for the production of pesticides, herbicides, fungicides, plastics, surfactants, shampoos, liquid soaps, and emulsion agents. Nonetheless, widespread and large-scale utilization of organohalogens might negatively impact life quality as these compounds are toxic to organisms and persistently present in the environment. An effort to decrease the effect of MCA pollutant is by performing bioremediation, taking advantage of microorganisms that produce haloacid dehalogenases, a class of enzymes that catalyze the breakage of carbon halogen bonds. In this sense, we have isolated Klebsiella pneumoniae ITB1 that could degrade MCA. The haloacid dehalogenase gene from this bacterium has been successfully cloned into pGEM-T vector and subcloned into pET-30a(+) expression vector to yield pET-hakp1 recombinant clone in Escherichia coli BL21 (DE) host cell. This research aimed to find an optimum condition for producing haloacid dehalogenase from this recombinant clone using Response Surface Methodology (RSM). Among the independent variables studied were the concentration of inducer, incubation temperature after the induction, and incubation period after the induction. We obtained the crude extract of the enzyme as cells' lysate after sonicating the bacterial cells. Haloacid dehalogenase activity against MCA substrate was determined by measuring the amount of chloride ions released into the medium of the enzymatic reaction using the colorimetry method, according to Bergmann and Sanik. The result indicated that the optimum condition for haloacid dehalogenase production by E. coli BL21 (DE3)/pET-hakp1 was observed when using 1.8 mM IPTG (isopropyl-β-D-1-thiogalactopyranoside) as the inducer, followed by 4 h incubation with shaking at 37 °C, which was predicted to result in a maximum of 0.48 mM chloride ions from 0.50 mM of MCA substrate. This report provides an insight into applying RSM for optimization of enzyme production from E. coli recombinant clones.


Effect of triple line vs isoechogenic endometrial texture on pregnancy outcome following embryo transfer according to use of controlled ovarian stimulation (COH) or estrogen/progesterone replacement.
To determine if pregnancy rates following embryo transfer are reduced if the endometrial echo pattern in the late proliferative phase is isoechogenic (IE) vs triple line (TL). Pregnancy and implantation rates were compared according to TL vs IE pattern in the late proliferative phase in women having in vitro fertilization-embryo transfer (IVF-ET), frozen ET, and transfer of embryos derived from donor oocytes. There was no difference in pregnancy rates with IE vs TL pattern with fresh or frozen ET or in donor egg recipients. The degree of ovarian reserve did not affect the pregnancy rates according to endometrial echo pattern. The presence of an IE pattern in the late proliferative phase should not influence the treating physician to either cancel the cycle and withhold human chorionic gonadotropin (hCG) injection or freeze all embryos and defer transfer.


Protective effect of antibodies to two viral envelope glycoproteins on lethal infection with Newcastle disease virus.
The protective effect of humoral immunity against lethal infection of chickens with Newcastle disease virus was studied. Chickens hatched from eggs laid by hens vaccinated with live attenuated Newcastle disease virus vaccine possessed antibody to various components of the virus, and were resistant to a challenge with a virulent strain of Newcastle disease virus which was 100 per cent fatal for the offspring of nonvaccinated hens. Passive administration of antiserum raised against whole virions provided susceptible chickens protection comparable to that seen in the birds with maternal antibody. When administered passively, both anti-HN serum with virus neutralizing activity, and anti-F serum with only marginal virus neutralizing activity significantly prolonged the survival of infected birds but failed to achieve the level of protection as afforded by the anti-whole NDV serum. The protection provided by the simultaneous presence of anti-HN and anti-F serum was significantly greater than that afforded by either alone and comparable to that of anti-whole NDV serum, indicating the complementary effect of anti-HN and anti-F antibodies not only in cell cultures as reported previously (19), but also in a natural host.


Distribution, sources, and ecological risk assessment of polychlorinated biphenyls (PCBs) in the estuary of Dagu River, China.
Four different types of 0-30 cm soil/sediment samples were collected from aquaculture land, farmland, industrial land and river bottom sediment in the estuary area of Dagu River, and the pollution status and sources of 7 PCB congeners were analyzed. The results showed that the mean values of Σ7PCBs in soil/sediments of different land use types were 5.01 ng g-1 dw for industrial land, 3.6 ng g-1 dw for estuarine sediments, 2.09 ng g-1 dw for farmland soil and 1.78 ng g-1 dw for farming land. All samples were at low pollution levels and pose little ecological risks. PCBs in the samples are mainly comprised of highly chlorinated biphenyls, and their content decreases gradually with increasing sampling depth. Based on the principal component analysis, it is concluded that the main source of PCBs in the study area is shipping activities, in addition to atmospheric transport and sedimentation sources.


Factors affecting urea clearance during continuous hemodiafiltration in the canine model.
Continuous hemofiltration (CH) for the treatment of hypervolemia and electrolyte abnormalities in critically ill patients with acute renal failure has been shown to be an effective mode of therapy. This technique offers several advantages over peritoneal dialysis or hemodialysis: it is technically less complex, provides efficient ultrafiltration, and produces fewer hemodynamic disturbances. Recently, continuous hemodiafiltration (CHD) using a flow of dialysate fluid into the ultrafiltration chamber has been reported to augment urea clearance. The purpose of this study was to determine the blood flow and dialysate flow characteristics for optimal clearance of urea and creatinine using this technique. Six mongrel dogs (mean weight, 8.0 +/- 1.1 kg) underwent bilateral nephrectomy to induce anuric renal failure. Postoperatively, the animals were fluid resuscitated and fed ad libitum. Twenty-four hours following nephrectomy, venovenous hemofiltration was instituted. Blood flow was regulated via a roller pump, while dialysate flow was regulated using an infusion controller. An Amicon-30S hemofilter was used in the circuit. Blood flow rates of 5, 10, 15, 20, 25, and 30 mL/kg/min were used. Hemodiafiltration using Dianeal 1.5% solution was used in each animal. Net fluid losses via ultrafiltration were replaced using lactated Ringer's solution. Three of six animals survived for the complete five-hour hemofiltration period. No marked disturbances in electrolyte serum concentrations, including hyperkalemia, were observed. BUN concentrations were reduced by 35% and creatinine by 26%. Variation of the dialysate flow rate did not influence clearance of either urea or creatinine. Instead, clearance appeared to be flow dependent, and it was markedly increased at flow rates greater than 15 mL/kg/min.(ABSTRACT TRUNCATED AT 250 WORDS)


Radiotherapy of small intracranial tumours with different advanced techniques using photon and proton beams: a treatment planning study.
The potential benefits and limitations of five different radiation techniques, 3D conformal radiotherapy (3DCRT), stereotactic arc therapy (SRS/T), intensity modulated radiotherapy with photons (IMRT), and radiotherapy with protons (spot scanning (SSp) or passive scattering (PSp)), have been assessed using comparative treatment planning methods in a cohort of patients presenting with 'benign' brain tumours. Plans for five acoustic neurinomas, five meningiomas, and two pituitary adenomas were computed for all modalities using computed tomography (CT) scans to delineate planning target volume and organs at risk (OARs) and to predict dose distributions. Dose-volume histograms were used for physical and simple biological evaluation. Proton techniques were shown to be superior to all photon approaches for the irradiation of small brain lesions in terms of target dose uniformity and conformity and in terms of sparing OARs. No major differences were observed between the results of the photon techniques, which were generally good for target coverage. Minimum target doses ranged from 81% with SRS/T to 93% with IMRT. The volume receiving more than 95% of the dose ranged from 95% (SRS/T) to 99% (PSp). No clear patterns of coverage dependence upon target shape were observed. Maximum brain stem irradiation ranged from 60% with IMRT to 26% with protons and the conformity index from 4.4 with IMRT to 2.5 with protons. Considering the rather long life expectancy of the patients suffering from meningiomas, neurinomas, and pituitary adenomas, the most important aspect to be considered, other than target coverage, is toxicity and in the long term, the possibility of secondary tumour induction. Considering these aspects, proton irradiation should be the irradiation technique of choice, when available. If not, IMRT, or even 3DCRT, techniques can provide an acceptable compromise, even without recurring to unconventional treatments like SRS/T, which require complex installations and high machine occupancy.


ATP6V0C gene variants were identified in individuals with epilepsy, with or without developmental delay.
The cause of epilepsy with or without developmental disorders was unidentified in a significant proportion of patients. Whole exome sequencing was performed in three unrelated patients with early-onset epilepsy, with or without developmental delay and intellectual disability. We identified de novo heterozygous variants (p.Arg119Trp, p.Val99_Ser102del, c.260_263 + 11delinsGCCCA) in the ATP6V0C gene, which encodes a subunit of vacuolar ATPase. Three-dimensional protein modeling showed that the variant p.Arg119Trp in ATP6V0C affected the hydrogen bonds with the 115th and 123rd residues, and the protein stability. The p.Val99_Ser102del and c.260_263 + 11delinsGCCCA variants in the other two patients resulted in a loss of function with microdeletion or splicing effects. Their seizures and psychomotor developmental outcomes were different, and all patients had a good prognosis. Our study provides evidence that de novo heterozygous ATP6V0C variants are related to epilepsy and associated with or without developmental delay.


The Psychological Impact of Referral for Mammography Screening for Breast Cancer Among Women in Muscat Governorate: A cross-sectional study.
Breast cancer constitutes the majority of diagnosed cancers in Oman's females, accounting for 19.2%, which prompted the introduction of a breast cancer screening programme into the Omani healthcare system. There are rising international concerns about the effectiveness of mammography as a screening tool and its psychological impact. The current study aimed to determine the social, emotional and physical dysfunction caused by the waiting time from the day of scheduling the appointment until the day of screening and explore associated risk factors. This cross-sectional study was conducted between March and December 2017 at Khoula Hospital, Muscat, Oman, using a two-part self-administered questionnaire. Part one of the questionnaire collected clinical and demographic data. Part two consisted of the Psychological Consequences Questionnaire (PCQ) and focused on psychological consequences, measuring the effect of mammographic screening on emotional, physical and social functions. A total of 300 women aged ≥40 years old participated in this study (response rate: 100%). Results revealed that there was a minimal negative psychological impact from screening using mammograms. All PCQ domains were significantly impacted for participants who reported a family history of cancer (P = 0.007). The social score was significantly higher among women between 40-50 years old (P = 0.008). Scores of emotional and social functions were significantly affected by participants' employment status; employed women were more affected than those who were not (P = 0.043 and 0.012, respectively). However, women's levels of literacy did not affect any of the domains. The psychosocial impact of the waiting period between scheduling and undergoing mammography screening was minimal in the current sample. Future research should evaluate the psychosocial impact on patients at different recall times.


Ultrasonically actuated neural probes for reduced trauma and inflammation in mouse brain.
Electrical neural recordings measured using direct electrical interfaces with neural tissue suffer from a short lifespan because the signal strength decreases over time. The inflammatory response to the inserted microprobe can create insulating tissue over the electrical interfaces, reducing the recorded signal below noise levels. One of the factors contributing to this inflammatory response is the tissue damage caused during probe insertion. Here, we explore the use of ultrasonic actuation of the neural probe during insertion to minimize tissue damage in mice. Silicon neural microprobes were designed and fabricated with integrated electrical recording sites and piezoelectric transducers. The microprobes were actuated at ultrasonic frequencies using integrated piezoelectric transducers. The microprobes were inserted into mouse brains under a glass window over the brain surface to image the tissue surrounding the probe using two-photon microscopy. The mechanical force required to penetrate the tissue was reduced by a factor of 2-3 when the microprobe was driven at ultrasonic frequencies. Tissue histology at the probe insertion site showed a reduced area of damage and decreased microglia counts with increasing ultrasonic actuation of the probes. Two-photon imaging of the microprobe over weeks demonstrated stabilization of the inflammatory response. Recording of electrical signals from neurons over time suggests that microprobes inserted using ultrasound have a higher signal-to-noise ratio over an extended time period.


Endoscopic ultrasonography of tumours of the oesophagus and the stomach.
Endoscopic ultrasonography is one of the intracavitary ultrasound procedures, all of which have as their objectives the attainment - through the use on high frequencies - of high resolution, and the avoidance of disturbing air and bone. In the technique of endoscopic ultrasonography, a high-resolution ultrasonic transducer attached to the tip of an endoscope is introduced into the gastrointestinal tract, from where it becomes possible to represent the wall of the tract, and also its neighbouring organs. The last few years have shown that the procedure is capable, in principle, of meeting the expectations placed in it.


A comparison of health communication effectiveness and the improvement of management strategies: taking two Chinese traditional medicine hospitals' WeChat public accounts as examples.
In the light of "Internet plus", hospitals are following the trend of using mobile internet and adopting a strategy of spreading public health knowledge through mobile terminals. WeChat is a social media with the largest number of users in China. Its public account has become the most popular service among the public. We examine the health communication of medical institutions on social media platforms. The WeChat public accounts of Zhejiang Provincial Chinese Traditional Medicine Hospital and Jiangxi Provincial Chinese Traditional Medicine Hospital were taken as cases to measure the communication effect from the following dimensions: update interval, content positioning and design, numbers of clicks and likes as well as topic types. The update interval of WeChat public account of Jiangxi Provincial Hospital of Traditional Chinese Medicine was regular, compared with that of the other hospital. The accounts of the two hospitals both set up special sections to facilitate patients to obtain medical services online. There is an extremely significant difference between the two hospitals' mean numbers of clicks (p < 0. 001), compared with no significant difference between their mean numbers of likes. One-way analysis of variance suggests the type of topic on posts is significantly correlated with the number of clicks. Moreover, there is an extremely significant difference between public health knowledge and news propaganda. The development of hospitals' WeChat public accounts can promote people's health and equity in accessing medical information and service, and also boost "Internet plus health care" service. The topic type of hospital's news publicity is paid a relatively lower attention by users. Therefore, hospitals' WeChat public accounts need to adjust their strategy from propaganda-oriented to users-centered, with topic planning and posts designed to fulfill users' needs.


Heterologous protein secretion by Candida utilis.
The yeast Candida utilis (also referred to as Torula) is used as a whole-cell food additive and as a recombinant host for production of intracellular molecules. Here, we report recombinant C. utilis strains secreting significant amounts of Candida antarctica lipase B (CalB). Native and heterologous secretion signals led to secretion of CalB into the growth medium; CalB was enzymatically active and it carried a short N-glycosyl chain lacking extensive mannosylation. Furthermore, CalB fusions to the C. utilis Gas1 cell wall protein led to effective surface display of enzymatically active CalB and of β-galactosidase. Secretory production in C. utilis was achieved using a novel set of expression vectors containing sat1 conferring nourseothricin resistance, which could be transformed into C. utilis, Pichia jadinii, Candida albicans, and Saccharomyces cerevisiae; C. utilis promoters including the constitutive TDH3 and the highly xylose-inducible GXS1 promoters allowed efficient gene expression. These results establish C. utilis as a promising host for the secretory production of proteins.


[Antiangiogenic therapy for types I and II macular neovascularization in age-related macular degeneration].
The neovascular form of age-related macular degeneration (AMD) is characterized by growth of newly formed vessels, accumulation of fluid and, in most cases, presence of retinal pigment epithelium detachment. Depending on its localization in relation to retinal pigment epithelium (RPE), macular neovascularization (MNV) can be considered type 1 when it is located under the RPE, and type 2 when it is invading the RPE and the neurosensory part of the retina. To conduct a retrospective analysis of the use of anti-VEGF therapy in AMD patients with types I and II of MNV. The study enrolled 89 AMD patients (89 eyes) with active MNV who have been under observation for 3 years. In the course of treatment all patients underwent standard ophthalmological examination that included visometry, biomicroscopy and ophthalmoscopy with mydriasis, as well as optical coherence tomography. Anti-VEGF therapy was found to stabilize best corrected visual acuity (BCVA) in both types of MNV (I and II). Comparison of the intraretinal and subretinal fluids (IRF and SRF) revealed that initially neuroepithelium detachment is more frequent (approximately in 90% of eyes) than IRF (30-40%). Antiangiogenic therapy is associated with better resorption of SRF, by the third year of the follow-up the neuroepithelium detachment is visualized in 60% of patients, while IRF remains and is observed in 40% of cases. Antiangiogenic therapy has shown good functional and morphological effectiveness in both first and second types of MNV.


All Fatigue is Not Created Equal: The Association of Fatigue and Its Subtypes on Pain Interference in Orofacial Pain.
Fatigue is known to be a pathway through which depression, psychological distress, pain intensity, and sleep disturbance influence pain interference, but the independent effects of fatigue on pain interference after controlling for these variables remains unknown. In addition, no study to date has tested whether fatigue subtypes of general fatigue, mental fatigue, emotional fatigue, physical fatigue, or vigor differentially predict pain interference. The current study tested these associations using archival medical data of 2133 chronic orofacial pain patients, who completed a battery of psychological questionnaires at the time of their first appointment at an orofacial pain clinic. Hierarchical linear regression analysis revealed that after controlling for depression, psychological distress, sleep disturbance, pain intensity, and demographic variables, fatigue predicted higher pain interference (B=0.70, SE=0.17, P<0.001, η=0.01). Physical fatigue (B=1.70, SE=0.48, P<0.001, η=0.01) and vigor (B=-3.24, SE=0.47, P<0.001, η=0.03) were independently associated with pain interference after controlling for the aforementioned variables. The findings suggest that fatigue is an important independent predictor of pain interference and not merely a mediator. These findings also suggest that not all fatigue is created equal. Interventions aimed at reducing pain interference should target specific fatigue symptoms of physical fatigue and vigor. Future research investigating the independent associations of fatigue subtypes on pain outcomes may help clarify the nature of the interrelationships between pain and fatigue.


Metal contamination recorded in the sediment of the semi-closed Bakar Bay (Croatia).
This study presents metal levels in the sediments of the Bakar Bay, with its main goal to evaluate recent anthropogenic influence, as well as over previous decades. Sediment profiles at 7 sampling points were taken. Chemical contents in bulk sediment were obtained using ICP, ICP-MS, and AAS methodologies, and 20 most significant elements were presented. Concentrations of selected elements were evaluated by factor statistical analyses to identify their source. Also, metal enrichment factor and geoaccumulation index were calculated, and spatial distribution maps for three sediment layers were constructed. Measured metal concentrations in sediment were compared with concentrations in other sediments from the Adriatic Sea. In addition, a set of sediment quality guidelines were also applied in order to predict the probability of adverse biological effects on the benthic community: This was found not to be very serious. Factor analysis clearly demonstrates the segregation between metals of natural origin resulted from soil and bedrock weathering (Li, Al, Cr, Sc), and with two anthropogenic sources originating from the city of Bakar and bulk cargo terminal (Hg, Pb, Zn, Ag, Sn, and Fe). Mercury (max 0.65 μg g(-1)) is found to be the heaviest contaminant, followed by lead (max 71.5 μg g(-1)), copper (89.3 μg g(-1)), and zinc (156 μg g(-1)). However, this study shows that Bakar Bay is considerably less polluted with toxic metals than it was believed.


Open versus laparoscopic resection of primary tumor for incurable stage IV colorectal cancer: a large multicenter consecutive patients cohort study.
To investigate the hypothesis that laparoscopic primary tumor resection is safe and effective when compared with the open approach for colorectal cancer patients with incurable metastases. There are only a few reports with small numbers of patients on laparoscopic tumor resection for stage IV colorectal cancer. Data from consecutive patients who underwent palliative primary tumor resection for stage IV colorectal cancer between January 2006 and December 2007 were collected retrospectively from 41 institutions. Short- and long-term outcomes were compared between patients who underwent laparoscopic or open resection. A total of 904 patients (laparoscopic group: 226, open group: 678) with a median age of 64 years (range: 22-95) were included in the analysis. Conversion was required in 28 patients (12.4%) and the most common reasons for conversion (23/28: 82%) were bulky or invasive tumors. There was no 30-day postoperative mortality in either group. The complication rate (NCI-CTCAE grade 2-4) after laparoscopic surgery (17%) was significantly lower than that after open surgery (24%) (P = 0.02), and the difference was greater (4% vs 12%; P < 0.001) when we limited the analysis to severe (≥grade 3) complications. The median length of postoperative hospital stay in the laparoscopic group was significantly shorter than that in the open group (14 vs 17 days; P = 0.002). In univariate analysis, overall survival for the laparoscopic group was significantly better than that for open surgery (median survival time: 25.9 vs 22.3 months, P = 0.04), although no difference was apparent in multivariate analysis. Compared with open surgery, laparoscopic primary tumor resection has advantages in the short term and no disadvantages in the long term. It is a reasonable treatment option for certain stage IV colorectal cancer patients with incurable disease.


Comparison between support vector machine and deep learning, machine-learning technologies for detecting epiretinal membrane using 3D-OCT.
In this study, we compared deep learning (DL) with support vector machine (SVM), both of which use three-dimensional optical coherence tomography (3D-OCT) images for detecting epiretinal membrane (ERM). In total, 529 3D-OCT images from the Tsukazaki hospital ophthalmology database (184 non-ERM subjects and 205 ERM patients) were assessed; 80% of the images were divided for training, and 20% for test as follows: 423 training (non-ERM 245, ERM 178) and 106 test (non-ERM 59, ERM 47) images. Using the 423 training images, a model was created with deep convolutional neural network and SVM, and the test data were evaluated. The DL model's sensitivity was 97.6% [95% confidence interval (CI), 87.7-99.9%] and specificity was 98.0% (95% CI, 89.7-99.9%), and the area under the curve (AUC) was 0.993 (95% CI, 0.993-0.994). In contrast, the SVM model's sensitivity was 97.6% (95% CI, 87.7-99.9%), specificity was 94.2% (95% CI, 84.0-98.7%), and AUC was 0.988 (95% CI, 0.987-0.988). DL model is better than SVM model in detecting ERM by using 3D-OCT images.


Body ownership and the absence of touch: approaching the rubber hand inside and outside peri-hand space.
It is widely accepted that the integration of visual and tactile information is a necessity to induce ownership over a rubber hand. This idea has recently been challenged by Ferri et al. (Proc R Soc B 280:1-7, 2013), as they found that sense of ownership was evident by mere expectation of touch. In our study, we aimed to further investigate this finding, by studying whether the mere potential for touch yields a sense of ownership similar in magnitude to that resulting from actually being touched. We conducted two experiments. In the first experiment, our set-up was the classical horizontal set-up (similar to Botvinick and Cohen, Nature 391:756, 1998). Sixty-three individuals were included and performed the classical conditions (synchronous, asynchronous), an approached but not touched (potential for touch), and a 'visual only' condition. In the second experiment, we controlled for differences between the current set-up and the vertical set-up used by Ferri et al. (Proc R Soc B 280:1-7, 2013). Fifteen individuals were included and performed a synchronous and various approaching conditions [i.e., vertical approach, horizontal approach, and a control approach (no hands)]. In our first experiment, we found that approaching the rubber hand neither induced a larger proprioceptive drift nor a stronger subjective sense of ownership than asynchronous stimulation did. Generally, our participants gained most sense of ownership in the synchronous condition, followed by the visual only condition. When using a vertical set-up (second experiment), we confirmed previous suggestions that tactile expectation was able to induce embodiment over a foreign hand, similar in magnitude to actual touch, but only when the real and rubber hand were aligned on the vertical axis, thus along the trajectory of the approaching stimulus. These results indicate that our brain uses bottom-up sensory information, as well as top-down predictions for building a representation of our body.


Definitive palliation for neoplastic colonic obstruction using enteral stents: personal case-series with literature review.
Acute colonic obstruction due to malignancies is an emergency that requires surgical treatment. Elderly patients or inoperable tumors require intestinal decompression that is a simple colostomy in almost all cases. This "manoeuvre" leads the patient to a percentage of mortality/morbidity and to a bad quality of life due to acceptance of stoma. The introduction of enteral metal stent inserted endoscopically has, in our opinion, provided a new way to obtaining the definitive palliation of inoperable colo-rectal cancer with a simple method. We reported our case-series and we analyzed the current literature and costs of treatments.