The vitamin D3 pathway in human skin and its role for regulation of biological processes.
The skin is the only tissue yet known in which the complete ultraviolet-B (UV-B)-induced pathway from 7-dehydrocholesterol to hormonally active calcitriol (1alpha,25-dihydroxyvitamin D(3)) occurs under physiological conditions. Epidermal synthesis of calcitriol could be of fundamental relevance because calcitriol regulates important cellular functions in keratinocytes and immunocompetent cells. Because of their antiproliferative and prodifferentiating effects, calcitriol and other vitamin D analogs are highly efficient in the treatment of psoriasis vulgaris. The known antipsoriatic effect of UV-B light could, at least in part, be mediated via UV-B-induced synthesis of calcitriol. In addition, mounting evidence indicates that cutaneous vitamin D(3) synthesis is of high importance for the prevention of a broad variety of diseases, including various malignancies. New but controversially discussed sun-protection guidelines were established for the prevention of internal cancers. A better understanding of the metabolism of vitamin D in the skin opens new perspectives for therapeutic applications of vitamin D analogs.


[Double tachycardia (hisian and auricular) in a bradycardia-tachycardia syndrome (author's transl)].
The present case corresponds to a patient with a mitro-aortic valvulopathy of rheumatic origin with syncopal episodes and nauseas, who, in the ECG showed alternatively an extreme sinusal bradycardia and supraventricular tachyarrhythmias. It was interpreted as a typical case of bradycardia-tachycardia syndrome in which the crises of tachyarrhythmias consisted of episodes of double tachycardia with incomplete supra-hisian atrial-ventricular dissociation, documented by obtaining right atrial electrograms and hisian-electrograms during the episodes. Treatment was initiated with verapamil (10 mg intravenously every 8 hours) after an endocavitary pacemaker of demand had been placed. After 3 months the result was very satisfactory with good tolerance to the medical treatment and complete disappearance of the symptomatology.


Simulation study on carbon emission of China's freight system under the target of carbon peaking.
The development of Chinese society needs the support of a perfect and efficient freight transport system. Nonetheless, China's freight system is facing a major challenge in reducing carbon emissions. Hence, firstly, this paper explores three major internal drivers of carbon emissions by analyzing the current situation in China's freight system: proportion of railway freight (PORF), railway electrification level (REL) and electric truck penetration (ETP). Secondly, the system dynamics (SDs) model is used to simulate the carbon emission system of freight transportation in China. Thirdly, this paper sets 13 scenarios of carbon peaking to explore the paths of carbon peaking before 2030 under the three levels of development of ETP oriented freight system. The results indicate that when PORF, REL, and ETP reach 23.96% of total freight volume, 83.7% of rail freight, and 11% of truck freight in 2030 respectively, China's freight system has the most optimistic scenario of carbon peaking. Meanwhile, the time of carbon peaking is 2024, and the peak value is 0.842 billion tons. When PORF, REL, and ETP reach 15.96% of total freight volume, 63.7% of rail freight, and 3% of truck freight in 2030 respectively, China's freight system has the worst scenario of carbon peaking. Meanwhile, the time of carbon peaking is 2029, and the peak value is 1.016 billion tons. Also, it is proved that improving PORF, REL, and ETP is an effective way to achieve green and sustainable development of China's freight industry.


Integrating piezoresistive sensors on the embouchure analysis of the lower lip in single reed instrumentalists: implementation of the lip pressure appliance (LPA).
It is essential to understand, characterize, and measure the embouchure mechanism of a wind instrumentalists, where the applied forces on the perioral tissues can usually promote discomfort or pain. The sample consisted of five clarinet players and five saxophone players. The embouchure force measurements at the lower lip area were assessed using a piezoresistive sensor (FlexiForceTM, Tekscan, Boston, USA, 0.07 kgf/cm2) placed on the lower part of the mouthpiece of the single reed instrument. Furthermore, each participant performed three times three different notes at different pitches: high, medium, and low. An intraoral device was manufactured in order to dissipate the existing pressures. The piezoresistive sensors applied to the mouthpiece of the five clarinetists presented values between 16 and 226 g of force. In the case of the five saxophonists, the values registered were between 5 and 320 g of force. Piezoresistive sensors are a valid option to characterize that single reed instrumentalists apply substantial forces at the lower lip that can be equivalent to medium orthodontic forces. The implementation of the Lip Pressure Appliance can be a valid solution on the prevention of eventual lesions resulting from the embouchure forces.


Developing an empathy educational model (EEM) for undergraduate nursing students: A Delphi Technique.
Despite the growing benefits of empathy education for medical students, there is still a lack of formal empathy courses in the Chinese context. To develop an empathy educational model for undergraduate nursing students, the Delphi technique was used in this study. Experts were selected from different regions of China and invited to participate in the three rounds of consultation, via email. The final empathy educational model was comprised of nine themes and 44 subthemes. The nine themes included: a. Bring the learner to the empathic world; b. Introduce the basic knowledge of empathy; c. Master empathy skills; d. Practice empathy; e. Evaluate empathy ability; f. Follow-up support; g. Distribution of educational hours for teaching empathy; h. Forms of empathy training; and i. Student reflection on empathy education. Consensus was achieved among the experts on empathy educational content, using the Delphi Technique, which can provide a reference for the empathy training of university medical students. It is necessary to have the empathy educational model further applied and evaluated, in conjunction with intervention studies, in the future.


Can myometrial electrical activity identify patients in preterm labor?
The objective of the study was to determine whether myometrial electrical activity can differentiate false from true preterm labor. Electrical uterine myography (EUM) was measured prospectively on 87 women, gestational age less than 35 weeks. The period between contractions, power of contraction peaks and movement of center of electrical activity (RMS), was used to develop an index score (1-5) for prediction of preterm delivery (PTD) within 14 days of the test. The score was compared with fetal fibronectin (fFN) and cervical length (CL). Patients delivering within 14 days from testing showed a higher index and mean RMS (P = .000). No patients with EUM index scores of 1-2 delivered in this time frame. Combining EUM with CL or fFN increased predictability. Logistic regression revealed that history of PTD and EUM index had 4- to 5-fold increased risk for PTD. Gestational age at testing, body mass index, fFN, and CL were nonsignificant contributors to PTD risk. Measuring myometrial electrical activity may enhance identification of patients in true premature labor.


App-based mindfulness meditation reduces perceived stress and improves self-regulation in working university students: A randomised controlled trial.
We investigated whether a brief mindfulness meditation programme delivered via a smartphone app improves perceived stress, self-regulation and life satisfaction in part-time working university students. Mindfulness and cognitive reappraisal were analysed as potential mediators. A total of 64 university students working at least 20 h per week during the semester were randomised to either a mindfulness-based mobile intervention or a wait-list control condition. Participants in the intervention group were asked to complete one training session of 10-15 min per day using the app. Psychological measures were assessed via a self-report questionnaire at baseline and after 8 weeks. The online mindfulness programme was found to significantly decrease perceived stress (ηp 2 = .180, a large effect). It also increased self-regulation (ηp 2 = .195, a large effect), mindfulness (ηp 2 = .174; a large effect) and cognitive reappraisal (ηp 2 = .136, a medium effect). Increments in life satisfaction were not significant. Changes in self-regulation were mediated by increased mindfulness. Overall, the mobile application was effective in improving mental well-being and coping abilities in a non-clinical sample, encouraging further development of digital health treatments.


Patterns of lymphatic spread in rectal cancer. A topographical analysis on lymph node metastases.
The presence of lymph node (LN) metastases is the most important prognostic factor in rectal cancer. The exact LN status can only be known when an extended lymph node dissection (LND) has been performed, a process not routinely performed. If the likelihood of LN metastases can be more accurately assessed preoperatively, then an optimal multimodality treatment plan can be established. 605 patients with primary rectal cancer operated upon with wide LND (D3 level) were analysed for LN metastases combining topographical localisation and morphological features of the tumour. More distal rectal tumours tend to more LN metastases and more lateral lymphatic spread. Tumours >or=3 cm show more LN metastases compared with those smaller than 3 cm. Depth of bowel wall invasion is strongly related to the presence of LN metastases. The peritoneal reflection has no discriminating role in the mode of spread. Intra-operative assessment by the surgeon for presence of LN metastases is not reliable. When localisation, depth of bowel wall invasion and diameter of a rectal tumour are known, a likelihood of LN metastases can be assessed pre-operatively, not intra-operatively.


Surgical correction of refractory reflux esophagitis using the standard unmodified Belsey Mark IV technique.
The treatment of symptomatic hiatus hernia unresponsive to medical treatment has been refined in the last decade. The work of Hill and colleagues in investigating the pathophysiology of this problem, and the anatomical techniques developed by Dr. Nissen and Mr. Belsey, have reduced the recurrence rate in the surgical management of symptomatic hiatus hernia to the point where it is at least as low as that for surgically treated duodenal ulcer. The most commonly employed methods of surgical repair for symptomatic hiatus hernia are those advocated by Drs. Nissen and Hill and Mr. Belsey, which are superior to the many unmonitored methods employed in the past. Recently, the use of modifications of these techniques has been reported in the literature with short follow-up studies. The current communication relates one surgeon's experience treating 85 consecutive patients with refractory reflux esophagitis using the standard unmodified Belsey Mark IV repair as originally described by Mr. Ronald Belsey of Bristol, England. Details of this repair are presented.


Acute Complex Care Model: An organizational approach for the medical care of hospitalized acute complex patients.
Chronic diseases are the major cause of death (59%) and disability worldwide, representing 46% of global disease burden. According to the Future Hospital Commission of the Royal College of Physicians, Medical Division (MD) will be responsible for all hospital medical services, from emergency to specialist wards. The Hospital Acute Care Hub will bring together the clinical areas of the MD that focus on the management of acute medical patients. The Chronic Care Model (CCM) places the patient at the center of the care system enhancing the community's social and health support, pathways and structures to keep chronic, frail, poly-pathological people at home or out of the hospital. The management of such patients in the hospital still needs to be solved. Hereby, we propose an innovative model for the management of the hospital's acute complex patients, which is the hospital counterpart of the CCM. The target population are acutely ill complex and poly-pathological patients (AICPPs), admitted to hospital and requiring high technology resources. The mission is to improve the management of medical admissions through pre-defined intra-hospital tracks and a global, multidisciplinary, patient-centered approach. The ACCM leader is an internal medicine specialist (IMS) who summarizes health problems, establishes priorities, and restores health balance in AICPPs. The epidemiological transition leading to a progressive increase in "chronically unstable" and complex patients needing frequent hospital treatment, inevitably enhances the role of hospital IMS in the coordination and delivery of care. ACCM represents a practical response to this epochal change of roles.


Immunohistological analysis of B7-H4, IDO1, and PD-L1 expression and tumor immune microenvironment based on triple-negative breast cancer subtypes.
B7 homolog 4 (B7-H4) and indoleamine 2,3-dioxygenase (IDO1) are factors involved in the inhibition of antitumor activity and are new therapeutic targets for immune checkpoint therapy. Our study aimed to simultaneously investigate the interrelationship among B7-H4, IDO1 and programmed cell death ligand 1 (PD-L1) expression in triple-negative breast cancer (TNBC), including tumor immune microenvironment (TIME) and TNBC subtypes. Immunostaining for PD-L1, B7-H4, and IDO1 was performed on whole-slide sections of 119 cases of TNBC. The TIME was evaluated based on stromal tumor infiltrating lymphocytes (sTILs; %), pattern classification of TILs, tumor-stroma ratio (TSR), and tertiary lymphoid structure (TLS). TNBC subtypes were also determined by immunohistochemistry analysis of cytokeratin 5/6 and androgen receptor (AR) expression. B7-H4 expression was significantly higher in cases with a combined positive score cutoff of 5 for PD-L1 (clone 28-8; p = 0.021), inflamed TIL pattern (p = 0.007), and TLS ≥ 4 (p = 0.006). B7-H4 expression was higher in case of CK5/6 ≥ 10 (p = 0.035). The H-scores of AR and B7-H4 were inversely correlated (ρ = - 0.509, p < 0.001). B7-H4 and IDO1 expression levels were inversely correlated in cases with AR < 10 (ρ = - 0.354, p < 0.001). These results suggest that considering the TIL pattern and TLS and identifying the expression of PD-L1 and the basal-like type are useful for estimating B7-H4 expression. In addition, luminal androgen receptor (LAR)-type is frequently deficient in B7-H4 expression. In non-LAR types, B7-H4 and IDO1 expression are exclusive.


Microbiologic outcomes of ceftazidime-avibactam dosing in patients with sepsis utilizing renal replacement therapies.
The suggested dose of ceftazidime-avibactam (CEF/AVI) in patient with multidrug resistant organisms and utilizing renal replacement therapies (RRTs) is not validated in clinical studies. The objective of this study was to evaluate the microbiologic cure of bacteremia and pneumonia using the recommended CEF/AVI dosing in patients utilizing RRT. A retrospective observational study conducted at our institution between September 15, 2018 and March 15, 2022. The primary end point was to determine the microbiologic cure. The secondary end points were the clinical cure, 30-day recurrence, 30-day all cause mortality. Fifty-six patients met the inclusion criteria, 36 (64.3%) were males, the median age was 69 (59.5-79.3) years, and the median weight was 69 (60-83.8) kg. Pneumonia represented 34 (60.7%) of infections. Microbiologic cure was achieved in 32 (57%) subjects. However, clinical cure was achieved in 23 (71.9%) patients in the microbiologic cure group versus 12 (50%) in the microbiologic failure group (p = 0.094). The 30-day recurrence occurred in 2 (6.3%) patients in the microbiologic cure group versus 3 (12.5%) in the microbiologic failure group (p = 0.673). Further, the 30-day all-cause mortality was 18 (56.3%) versus 10 (41.7%) in both groups respectively (p = 0.28). The most used dose in patients utilizing continuous veno-venous hemofiltration (CVVH) was 1.25 g q8h, while the dose was 1.25 g q24h in those who utilized intermittent hemodialysis (IHD). The multivariate logistic regression indicated that bacteremia (OR 41.5 [3.77-46]), Enterobacterales (OR 5.4 [1.04-27.9]), and the drug daily dose (OR 2.33 [1.15-4.72]) were independently associated with microbiologic cure. Microbiologic cure of ceftazidime-avibactam in patient utilizing CVVH and IHD is dependent on bacteremia diagnosis, the drug daily dose, and bacterial species. These findings need to be replicated in a larger prospective study, with no recommendations in those utilizing RRT.


Interaction of anticancer drug mitoxantrone with DNA hexamer sequence d-(CTCGAG)2 by absorption, fluorescence and circular dichroism spectroscopy.
The interaction of mitoxantrone with d-(CTCGAG)2 has been studied by absorption, fluorescence and circular dichroism (CD) spectroscopy. The hypochromism and quenching of fluorescence showed that about four mitoxantrone molecules may be binding externally to DNA hexamer sequence at high drug to nucleic (D/N) acid duplex ratios (28.0-1.1). At lower D/N ratios (1.0-0.2), a red shift in absorption maxima at 610 and 660 nm by 15 and 20 nm, respectively and a red shift in emission maxima by 11 nm accompanied by increase in absorbance and emission has been observed. The equilibrium constant for binding at low (1.0-0.2) and high (28.0-1.1) D/N ratios is 1.8×10(5) M(-1) and 1.38×10(6) M(-1), respectively. The CD spectra show change in intensity of bands accompanied by appearance of induced bands at 325 nm and 650-700 nm. The 251 nm band shows blue shift at D/N ratio of 0.25 and 0.5. The binding isotherms show stoichiometry of 0.25 and 0.5 mitoxantrone molecules binding per duplex. The results suggest stacking of aromatic chromophore of mitoxantrone with terminal base pair of DNA strand forming a sandwiched structure of mitoxantrone between four and two duplex molecules. These investigations are relevant to the formation of ternary complex with topoisomerase enzyme and hence an understanding of anti tumor action of mitoxantrone.


Sexual activity and lower urinary tract symptoms.
Lower urinary tract symptoms (LUTS) have a profound impact on women's physical, social, and sexual well being. The LUTS are likely to affect sexual activity. Conversely, sexual activity may affect the occurrence of LUTS. The aims of the study were to elucidate to which extent LUTS affect sexual function and to which extent sexual function affect LUTS in an unselected population of middle-aged women in 1 year. A questionnaire was sent to 4,000 unselected women aged 40-60 years. All 2,284 women (57.1%) who completed a baseline questionnaire and a similar questionnaire 1-year later were included. Data comprised age, occurrence of LUTS, hormonal status, and sexual activity. A multiple conditional logistic regression model was used to analyze the relationship between sexual activity and LUTS adjusted for age and hormonal status. At baseline and 1-year later, 49 women (2.2%) had no sexual intercourse, and 298 women (13.0%) either ceased or resumed sexual relationship. Compared to women having sexual relationship, a statistically significant three to sixfold higher prevalence of LUTS was observed in women with no sexual relationship. In women who ceased sexual relationship an increase, although not statistically significant, in the de novo occurrence of most LUTS was observed. In women who resumed sexual relationship an insignificantly decrease in LUTS was observed. In women whose sexual activity was unchanged no change in the occurrence of LUTS was observed. Our study confirms a close association between sexual activity and the occurrence of LUTS. A hypothesis that sexual inactivity may lead to LUTS and vice versa cannot be rejected.


Mitogenome of the extinct Desert 'rat-kangaroo' times the adaptation to aridity in macropodoids.
The evolution of Australia's distinctive marsupial fauna has long been linked to the onset of continent-wide aridity. However, how this profound climate change event affected the diversification of extant lineages is still hotly debated. Here, we assemble a DNA sequence dataset of Macropodoidea-the clade comprising kangaroos and their relatives-that incorporates a complete mitogenome for the Desert 'rat-kangaroo', Caloprymnus campestris. This enigmatic species went extinct nearly 90 years ago and is known from a handful of museum specimens. Caloprymnus is significant because it was the only macropodoid restricted to extreme desert environments, and therefore calibrates the group's specialisation for increasingly arid conditions. Our robustly supported phylogenies nest Caloprymnus amongst the bettongs Aepyprymnus and Bettongia. Dated ancestral range estimations further reveal that the Caloprymnus-Bettongia lineage originated in nascent xeric settings during the middle to late Miocene, ~ 12 million years ago (Ma), but subsequently radiated into fragmenting mesic habitats after the Pliocene to mid-Pleistocene. This timeframe parallels the ancestral divergences of kangaroos in woodlands and forests, but predates their adaptive dispersal into proliferating dry shrublands and grasslands from the late Miocene to mid-Pleistocene, after ~ 7 Ma. We thus demonstrate that protracted changes in both climate and vegetation likely staged the emergence of modern arid zone macropodoids.


Enhancement of repair replication in mammalian cells by hydroxyurea.
The effect of hydroxyurea on DNA repair replication has been studied in Chinese hamster ovary cells. Mitotic cells were treated with UV irradiation, methyl methanesulfonate or nitrogen mustard and incuated in the presence of each of the 4 [3H] deoxyribonucleosides plus BrdUrd and FdUrd for 2 h. The amount of repair replication was quantitated on CsCl gradients and similar values were obtained for each nucleoside. In all cases addition of HU during the incubation period increased these values approximately 2-fold. Following MMS treatment, pool sizes for each of the nucleosides were estimated by varying the amount of exogenously supplied nucleoside. They were found to be insensitive to the addition of HU and it is concluded that the increased incorporation of [3H]deoxyribonucleosides in the presence of HU reflects an increased amount of repair replication.


The role of the sodium pump in the developmental regulation of membrane electrical properties of cerebellar Purkinje neurons of the rat.
The postnatal development of the rat cerebellum has been well described morphologically and functionally. However, information regarding the electrical characteristics of Purkinje neurons during development is sparse. Using standard intracellular recording, the basic electrical properties of Purkinje neurons in cerebellar slices were compared at different postnatal ages. There was a significant, progressive increase in the resting membrane potential (RMP) of Purkinje neurons with age as well as a small but significant decrease in the cellular input resistance (Rin). The cardiac glycoside, ouabain (1 mM), an inhibitor of the sodium pump, depolarized Purkinje neurons significantly more with age. The magnitude of the increase in depolarizing activity of ouabain was equivalent to the magnitude of the increase in membrane potential. The number of ouabain binding sites was also found to increase with age suggesting an age related increase in the number of sodium pump sites. These results suggest that the predominant cellular mechanism which underlies the increase in membrane potential of Purkinje neurons during development is an increase in the density of Na+, K+ pump sites and in the contribution of the electrogenic sodium pump.


A compact pulse-modulation cold air plasma jet for the inactivation of chronic wound bacteria: development and characterization.
A compact low-temperature plasma jet device was developed to use ambient air as plasma gas. The device was driven by a 2.52-kV high-voltage direct-current pulse in a burst mode, with a repetition rate of 2 kHz. The maximum plasma discharge current was 3.5 A, with an approximately 10 ns full-width half-maximum. Nitric oxide, hydroxyl radical, atomic oxygen, ozone, and hydrogen peroxide-important reactive oxygen and nitrogen species (RONS)-were mainly produced. The amount of plasma-generated RONS can be controlled by varying the pulse-modulation factors. After optimization, the plasma plume length was approximately 5 mm and the treatment temperature was less than 40 °C. The preliminary bactericidal effects were tested on Staphylococcus aureus, Pseudomonas aeruginosa, and methicillin-resistant S. aureus (MRSA), and their biofilms. The results showed that the plasma can effectively inactivate S. aureus, P. aeruginosa, and MRSA in both time- and pulse-dependent manner. Thus, this produced plasma device proved to be an efficient tool for inactivating deteriorating bacteria. Further versatile utilization of this portable plasma generator is also promising.


Research priorities in hereditary hemochromatosis.
The Working Group on Research Priorities used a formal nominal group technique to identify and prioritize the specific aims of applied research needed to provide the scientific basis for population screening for iron overload disorders. The most important applied research goal was characterization of the natural history of the relation between genotype and phenotype in hereditary hemochromatosis and other iron overload disorders. Three other important research objectives were development of an optimal approach to screening for iron overload; analyses of the cost-effectiveness of screening; and assessment of the ethical, legal, and social implications of screening. To achieve these specific aims, two research studies were recommended as being of the highest priority: a multicenter, cross-sectional, population-based study of the natural history of iron overload and a multicenter, case-control study of patients with disease manifestations potentially attributable to hereditary hemochromatosis in primary care and subspecialty clinics.


Palliative Care Consultation in Hospitalized Patients With COVID-19: A Retrospective Study of Characteristics, Outcomes, and Unmet Needs.
Few studies have described the characteristics and palliative care needs in hospitalized patients with coronavirus disease 2019 (COVID-19). Describing characteristics, consultation demands, patients' needs, and outcomes of hospitalized patients with COVID-19 who received a palliative care evaluation. Retrospective chart review of patients (aged 18+ years) with COVID-19 admitted to an academic quaternary center and seen by the geriatrics and palliative medicine team from March 1st to May 11th, 2020. Socio-demographics, operational metrics, severity of illness, goals of care-advanced care planning documentation, and outcomes were analyzed. Three hundred seventy-six (17.6%) out of 2138 COVID-19 admissions were seen by the consultation team. Compared with prepandemic situation (September 1st, 2019, to February 29th, 2020), overall new consults (205 vs. 371, P < 0.001) significantly increased, particularly in the intensive care unit (ICU; 9.5% vs. 36.9%, P < 0.001). For the COVID-19 population, median age was 78 years (interquartile range, 70-87; range, 36-102); 56% were male. LACE score, D-dimer, and C-reactive protein suggested severe disease and increased risk of mortality. Seventy-five percent of consults were for goals of care-advanced care planning, and 9.6% for symptoms. During the index admission, 7.1% had documented advanced directives, and 69.7% became do not resuscitate. Of all deaths, 55.5% were in the ICU, and 87.2% were aged ≥65 years. Underserved minority patients had a disproportionate mortality. Overall consultation mortality (38.3% vs. 70.4%, P < 0.001) and ICU mortality (55.2% vs. 78.1%, P < 0.001) significantly increased compared with those before COVID-19. During this pandemic, understanding inpatient specialized palliative care needs and the vulnerable populations driving these causes may encourage health-care agencies and local, state, and federal governments to support the dedicated palliative care workforce.


Medication-related factors associated with proton pump inhibitor prescription beyond official guidelines in older adults.
To investigate the relationship between medications with a known risk of gastrointestinal bleeding and proton pump inhibitor (PPI) prescription not according to guidelines. An analysis of the records of 592 hospitalised patients aged 65 years or older was undertaken. The number of all medicines, potentially inappropriate medicines according to the EU(7)-PIM list and the Beers Criteria 2019 and medicines with a known risk of gastrointestinal bleeding, was compared in patients with PPI prescription not given based on guidelines and in patients with no PPI prescription. Patients prescribed PPI not based on guidelines used more medications on average (9.6 vs. 6.4, p < 0.001), more PIMs according to the EU(7)-PIM list (2.4 vs. 1.1, p < 0.001) and the Beers criteria (2.0 vs. 0.6, p < 0.001) at hospital admission and at discharge (8.9 vs. 7.5, p < 0.001, mean number of medications), (2.0 vs. 1.2, p < 0.001, EU(7)-PIM list), (1.9 vs. 0.8, p < 0.001, Beers criteria) than patients with no PPI prescription. Patients prescribed PPI not according to guidelines were more frequently using direct oral anticoagulants (28% vs. 12.8%, p < 0.001), corticosteroids (5.3% vs. 0.7%, p = 0.025) at hospital admission and at discharge (25.9% vs. 16.5%, p = 0.018, oral anticoagulants), (6.6% vs. 1%, p = 0.006, corticosteroids), (13.3% vs. 5.4%, p = 0.004, warfarin) than patients with no PPI prescription. The number of medications, potentially inappropriate medications according to the EU(7)-PIM list and Beers criteria, and the use of direct oral anticoagulants, warfarin and corticosteroid prescriptions were the medication-related factors associated with PPI prescription not according to guidelines in elderly patients.


Long-Term Results of Periacetabular Rotational Osteotomy Concomitantly With Arthroscopy in Adult Acetabular Dysplasia.
Although the long-term results of periacetabular osteotomy in acetabular dysplasia have been well documented, there is paucity in reports on the long-term outcomes of periacetabular osteotomy with simultaneous hip arthroscopy. This study aimed to assess the cumulative 10-year outcomes of periacetabular rotational osteotomy with concomitant hip arthroscopy. Through an arthroscopic procedure, the status of the labrum was assessed, and torn labrum was debrided. Evaluations on survival from conversion to total hip arthroplasty and success in radiographic and clinical long-term results were completed in 39 hips (36 patients). Acetabular parameters (center-edge angle, Sharp angle, acetabular-head index, and head lateralization index), Tönnis grades on radiograph, Harris Hip Score, and range of motion of the hip were evaluated. Survivorship analyses were evaluated with the Kaplan-Meier method. Thirty-eight hips (97.4%, 95% confidence interval 0.832-0.996) were preserved for 12.8 ± 1.7 years on average, and only 1 hip was converted to total hip arthroplasty at 7.8 years. All the acetabular parameters were improved (P < .001). Twenty-eight hips (71.8%) showed unchanged or improved Tönnis grades at the latest follow-up. The average Harris Hip Score was significantly better than the preoperative value (P < .001), and range of motion was not significantly different until the latest follow-up. Sufficient acetabular reorientation, such as periacetabular rotational osteotomy, with concomitant arthroscopic debridement showed successful long-term outcomes for acetabular dysplasia in adults.


Augmentation of anticancer effect with angiotensin II in intraarterial infusion chemotherapy for breast carcinoma.
We investigated the effect of angiotensin II (AT II) on blood flow in breast cancer patients using 81mKr and found that it increased tumor blood flow 2.3-fold while decreasing blood flow in adjacent normal tissue 0.7-fold. We, then, used AT II in conjunction with intraarterial infusion chemotherapy (IAC) for locally advanced breast cancer in order to increase drug delivery to the tumor and enhance its anticancer effect. Eleven patients (from 1976-1981) received IAC with doxorubicin through the internal thoracic and subclavian arteries, alternately, for 10 days (AT II- group). Twenty-four patients (from 1981-1985) received IAC with doxorubicin and concomitant infusion of AT II (1.3 micrograms/min through the internal thoracic artery and 2.6 micrograms/min through the subclavian artery) (AT II+ group). The response rate of the primary breast tumor was higher in the AT II+ group (92%) than in the AT II- group (73%) (P = 0.66). Complete tumor necrosis was 46% in the AT II+ group, but only 27% in the AT II- group (P = 0.51). These preliminary results suggest that the anticancer effect of IAC for breast cancer can be enhanced with concomitant infusion of AT II.


Preparation of single molecules and supramolecular complexes for high-resolution metal shadowing.
We have compared the appearance and preservation of molecular and supramolecular structures in preparations that were dried in vacuo at room temperature or freeze-dried. Fibrinogen and brain spectrin molecules appear similar in both types of preparation provided that drying at room temperature is performed in the presence of glycerol, which results in an even and reproducible distribution of such molecules (Shotton et al., 1979, J. Mol. Biol. 131, 303-329; Fowler and Erickson, 1979, J. Mol. Biol. 134, 241-249). In the case of crystalline actin sheets, actin filaments, and keratin filaments, freeze-drying preserves structural details that are often completely lost during drying at room temperature, whether or not glycerol is used. On the other hand, keratin filaments prepared by drying in the presence of glycerol display a beaded axial repeat that is probably due to "glycerol decoration." We conclude that although freeze-drying has no clear advantage over glycerol spraying/vacuum-drying in the case of single extended molecules, it may provide insight into the multiple effects of glycerol in specimen preparation. In the case of supramolecular assemblies such as filaments or crystalline sheets, freeze-drying preserves significantly more substructure and surface detail. The loss of such detail during drying at room temperature, probably through collapse phenomena such as distortion and flattening, cannot be prevented by glycerol.


Outcome of late probing for congenital nasolacrimal duct obstruction in Singapore children.
To evaluate the outcome of late probing in a mixed Asian children population with congenital nasolacrimal duct obstruction (CNLDO) and whether probing was associated with an increased risk of infection. A retrospective clinical study was conducted. A clinical diagnosis of CNLDO was defined in an infant who presented with a history of tearing and/or eye discharge up to 1 year of age with no other accompanying ocular pathology. All patients with a presumed diagnosis of CNLDO who had probing after 12 months of age were included in our study. Prior to probing, most patients had a trial of conservative treatment with massage and/or topical antibiotics. Intra-operative patency of probing was determined when metal to metal contact of the probe and forceps was achieved and/or when fluorescein dye was recovered from the nose after syringing. Successful probing was defined as a resolution of symptoms within 1 month after probing. Seventeen patients involving 19 eyes fulfilled our inclusion criteria for this study. Fourteen (82%) infants were Chinese, two Malays (12%) and the remaining one Indian (6%). There were 10 males (59%) and 7 females (41%) and the mean age at probing was 2.2 years (range, 14 months to 5 years 6 months). The subjects were followed-up post-operatively for a mean duration of 21.2 months (range, 2 months to 8 years). Successful probing in our series was 89.5% (17/19 eyes). Of the two eyes with persistent tearing, one resolved with massage about 9 months after the unsuccessful probing; the other was referred to the oculoplastic service for further management. Late probing after 13 months old appears to be an effective approach in the management of CNLDO in Asian infants.


Unusual presentation of tuberculous meningitis.
We present 4 cases of tuberculous meningitis with atypical clinical features and CSF findings. Two patients had initially normal CSF examination, one developed internuclear ophthalmoplegia, while the other had deterioration of consciousness. The third patient presented with paranoid psychosis, and the fourth had a picture mimicking acute bacterial meningitis and he developed right hemianopia due to a tuberculoma detected by MRI. All recovered completely with anti-tuberculous treatment.


Identifying single-nucleotide polymorphisms responsible for the linkage signal of rheumatoid arthritis on chromosome 6 by joint modeling of linkage and association.
This study evaluated the utility of unrelated controls and flanking markers when performing joint modeling of linkage and association by the LAMP software (version 0.0.6) [Am J Hum Genet 2005, 76:934-949; Am J Hum Genet 2006, 78:778-792]. Analyses were conducted on the simulated rheumatoid arthritis (RA) data in Genetic Analysis Workshop 15 (GAW15), using single-nucleotide polymorphisms (SNPs) on chromosome 6 over the 100 simulated replicates. We found that the LOD score for testing association in the presence of linkage dramatically increased when unrelated controls were added to affected sib pairs (ASPs), and that choosing a sufficient number of flanking markers is critical in order to distinguish between perfect linkage disequilibrium (which leads to the conclusion of a measured SNP explaining a linkage signal) and incomplete linkage disequilibrium (which leads to the conclusion of other undetected causal variants in a linkage region).


Prevalence and trends for Aboriginal and Torres Strait Islander children living with cerebral palsy: A birds-eye view.
To provide a birds-eye view of the trends of cerebral palsy (CP) for Australian Aboriginal and Torres Strait Islander children and young adults. Data were obtained for this population-based observational study from the Australian Cerebral Palsy Register (ACPR), birth years 1995 to 2014. The Indigenous status of children was classified by maternal Aboriginal and Torres Strait Islander or non-Indigenous status. Descriptive statistics were calculated for socio-demographic and clinical characteristics. Prenatal/perinatal and post-neonatal birth prevalence was calculated per 1000 live births and per 10 000 live births respectively, and Poisson regression used to assess trends. Data from the ACPR were available for 514 Aboriginal and Torres Strait Islander individuals with CP. Most children could walk independently (56%) and lived in urban or regional areas (72%). One in five children lived in socioeconomically disadvantaged remote/very remote areas. The birth prevalence of prenatal/perinatal CP declined after the mid-2000s from a high of 4.8 (95% confidence interval 3.2-7.0) to 1.9 per 1000 live births (95% confidence interval 1.1-3.2) (2013-2014), with marked declines observed for term births and teenage mothers. The birth prevalence of CP in Aboriginal and Torres Strait Islander children in Australia declined between the mid-2000s and 2013 to 2014. This birds-eye view provides key stakeholders with new knowledge to advocate for sustainable funding for accessible, culturally safe, antenatal and CP services. Birth prevalence of cerebral palsy (CP) is beginning to decline for Aboriginal and Torres Strait Islanders. Recent CP birth prevalence for Aboriginal and Torres Strait Islanders is 1.9 per 1000 live births. Most children with CP live in more populated areas rather than remote or very remote areas. One in five Aboriginal and Torres Strait Islander children with CP live in socioeconomically disadvantaged remote areas.


The burden of diabetic emergencies on the resuscitation area of a district-level public hospital in Cape Town.
Diabetes and its complications continue to cause a daunting and growing concern on resource-limited environments. There is a paucity of data relating to the care of diabetic emergencies in the emergency centres of entry-level hospitals in Africa. The aim of this study was to describe the burden of diabetic emergencies presenting to the emergency centre of an urban district-level hospital in Cape Town, South Africa. The Khayelitsha Hospital Emergency Centre database was retrospectively analysed for patients presenting with a diabetic emergency within a 24-week randomly selected period. The database was supplemented by a retrospective chart review to include additional variables for participants with diabetic ketoacidosis (DKA), uncomplicated hyperglycaemia, severe hypoglycaemia and hyperosmolar hyperglycaemic state (HHS). Summary statistics are presented of all variables. The prevalence of all diabetic emergencies was 8.1% (197/2424) (DKA n = 96, 48.7%; uncomplicated hyperglycaemia n = 45, 22.8%; severe hypoglycaemia n = 44, 22.3%; HHS n = 12, 6%). The median age was 48 years, with those presenting with DKA being substantially younger (36 years). A likely precipitant was identified in 175 (88%) patients; infection was the most common precipitant (n = 79, 40.1%). Acute kidney injury occurred in 80 (40.6%) cases. The median length of stay in the resuscitation area was 13 h (IQR 7.2-24) and 101 (51.3%) participants represented with a diabetic- related emergency within six months of the study period. The overall mortality rate was 5% (n = 10). This study highlights the high burden of diabetic emergencies on the provision of acute care at a district-level hospital. The high prevalence of diabetic emergencies (8%) consisted of DKA (48.7%), uncomplicated hyperglycaemia (22.8%), severe hypoglycaemia (22.3%), and HHS (6%). The high infection rate (40%) and the high percentage of patients returning with a diabetic emergency (51%) could be indicative of the need for improved community-based diabetic programmes.


LncRNA TPTEP1 inhibits the migration and invasion of gastric cancer cells through miR-548d-3p/KLF9/PER1 axis.
Despite the development of many methods and new therapeutic agents, the survival and prognosis of patients with gastric cancer are still poor. The role of TPTEP1 in gastric cancer has not been reported. Wound healing assay and transwell assay analysis TPTEP1/miR-548d-3p/KLF9/PER1 effect on migration and invasiveness of gastric cells. Western blot and RT-qPCR certificate TPTEP1/miR-548d-3p/KLF9/PER1transcription and expression of migration and invasion related genes. Luciferase assay was used to determine the adsorption of miR-548d-3p by TPTEP1 sponge, the targeting of miR-548d-3p to KLF9, and the binding of KLF9 to the promoter of PER1. immunohistochemical assay and H&E staining prove the function of TPTEP1 and miR-548d-3p in nude mice model of gastric cancer. TPTEP1 inhibited its expression by sponge adsorption of miR-548d-3p. miR-548d-3p targets KLF9 3'UTR to inhibit its expression, and KLF9 binds to the PER1 promoter to promote its expression.TPTEP1/KLF9/PER1 inhibits gastric cancer cell migration and invasion, and miR-548d-3p does the opposite. Our data suggest that TPTEP1 affects gastric cancer progression by regulating the miR-548d-3p/KLF9/PER1 axis. Targeting this pathway may provide new therapeutic opportunities for gastric cancer.


Layer-by-layer functionalized porous Zinc sulfide nanospheres-based solid-phase extraction combined with liquid chromatography time-of-flight/mass and gas chromatography-mass spectrometry for the specific enrichment and identification of alkaloids from Crinum asiaticum var. sinicum.
The current widely utilized polymer or C8, C18 end-capped material-based sorbents for solid-phase extraction could not capture alkaloids well only based on "like dissolves like" principle. In this paper, a layer-by-layer functionalized porous Zinc sulfide nanospheres-based solid-phase extraction (SPE) combined with liquid chromatography time-of-flight/mass spectrometry (LC-TOF/MS) and gas chromatography-mass spectrometry (GC-MS) was developed for the specific enrichment and identification of alkaloids from complex matrixes, Crinum asiaticum var. sinicum crude extracts. The functionalized porous Zinc sulfide nanospheres were prepared by the amidation reaction of poly-(acrylic acid) (PAA) homopolymer with amino groups onto the porous ZnS nanospheres. Tandem LC-TOF/MS spectrometry presented that the almost all of the twenty-three main peaks in elution fraction from the SPE could be inferred as alkaloids with ion of mass according to the nitrogen rule and hit formula with Peak View1.2@software from AB SCIEX, and seven alkaloids including two new found chemical entities were directly identified from their GC-MS spectra and retention indices. We believe that this SPE protocol can also be utilized in the future to selectively enrich alkaloids from extracts of other plant species.


Weight loss therapy for clinical management of patients with some atherosclerotic diseases: a randomized clinical trial.
The prevalence and burden of atherosclerotic (AS) diseases are increasing during the last twenty years. Some studies show a close relationship between overweight and AS, but influence on AS diseases of different weight loss methods are still studying. The purpose of the research was to study the effectiveness of a weight loss program in AS patients in randomized controlled trial, and to develop a conception of evolution of AS. A randomized controlled prospective clinical trial including 97 people, from them 71 patients with various AS manifestations. Patients were divided in 2 subgroups for non-drug weight loss program, and conventional drug therapy. The weight loss program included calorie restriction with 100-150 kcal/day, fat-free vegetables, salt diet, and optimum physical activity. Statistical analysis was performed using SPSS for Windows version 17.0. The weight loss subgroup lost ranging between 7-20% from an initial weight (P = 0.016). Weight loss was achieved due to fatty mass reduction only (P = 0.005). Hemoglobin levels (P < 0.001), bone mineral density (P < 0.001), percentages of water (P = 0.006) and muscle masses (P = 0.0038) were increased in weight loss subgroup. Ejection fraction (P < 0.0001), systolic output (P < 0.0001) were increased in patients with coronary artery disease. The weight loss program led to a decrease in symptomatic drugs doses up to total abolition. A conception of AS was developed. The weight loss program treated the AS diseases; improved laboratory and instrumental parameters, decreased symptomatic drugs doses. AS development is a logical way of ontogenetic ageing of body fat. ClinicalTrials.gov NCT01700075. State registration is # 0109RK000079, code is O.0475 at the National Center for Scientific and Technical Information of the Republic of Kazakhstan.


Unmanipulated haploidentical haematopoietic cell transplantation with radiation-free conditioning in Fanconi anaemia: A retrospective analysis from the Chinese Blood and Marrow Transplantation Registry Group.
Haematopoietic cell transplantation (HCT) is the only curative treatment for haematological complications in patients with Fanconi anaemia (FA). Haploidentical (haplo-) HCT is a promising alternative for FA. We aimed to analyse the outcomes of unmanipulated haplo-HCT in patients with FA with radiation-free conditioning. A total of 56 patients from 11 centres between 2013 and 2021 in China were retrospectively analysed. The mean (SD) cumulative incidence was 96.4% (0.08%) for 30-day neutrophil engraftment and 85.5% (0.24%) for 100-day platelet engraftment. With a median (range) follow-up of 2.4 (0.2-5.8) years, favourable mean (SD) overall survival of 80.9% (5.5%) and event-free survival of 79.3% (5.6%) were achieved. The mean (SD) incidences of acute graft-versus-host disease (aGvHD) Grade II-IV and Grade III-IV were 55.4% (0.45%) and 42.9 (0.45%) respectively. The mean (SD) cumulative incidence of 3-year chronic graft-versus-host disease (cGvHD) was 34.7% (0.86%) and that of moderate-to-severe cGvHD was 9.0% (0.19%). Our data demonstrate that in unmanipulated haplo-HCT for patients with FA, radiation-free regimens based on fludarabine and low-dose cyclophosphamide ± busulfan achieved favourable engraftment and survival with relatively high incidences of aGvHD and cGvHD. These results prompt the use of low-intensity conditioning without radiation and intensive GvHD prophylaxis when considering unmanipulated haplo-HCT in patients with FA.


Parental awareness of the implications of myopia and strategies to control its progression: A survey-based study.
Myopia has emerged as a significant public health concern. Effective methods have now been developed to delay its onset and progression. However, this information may not be reaching parents, and they are key players in terms of implementing the necessary preventive measures. This study investigated parental awareness of myopia, its implications and the strategies available for controlling it. A self-administered online survey was distributed to parents of children 6-16 years of age. To be eligible to respond, their child had to be myopic or at risk of developing myopia due to family history. A total of 330 parents completed the survey, of which 321 were included for analysis. Sixty-seven percent of respondents had at least one myopic son/daughter, and most were between -1.00 and -1.75 D. Among parents of myopic children, 20.9% thought that their child's myopia progressed moderately. Sixty-seven percent of parents had a significant level of concern about the progression of the myopia and felt that it was caused mainly by the use of electronic devices and genetics. A generalised linear model showed that parental concern was significantly predicted by the perception of evolution (p < 0.001) and the number of known health-related consequences (p < 0.001). Almost 40% of parents were unaware of the existence of myopia control strategies. Relatives and eye care practitioners are the main sources of information. The most well-known myopia control strategy was myopia control soft contact lenses (29.2%), although the option that most parents would opt for was spectacles with peripheral defocus lenses (47.1%). The selection of a contact-lens-based myopia control method correlated significantly with the age of the children (p < 0.001). Society in general and parents in particular need more information about myopia, its consequences and the options available for its control. Eye care practitioners play an important role in this issue.


Metastatic Breast Cancer Recurrence after Bone Fractures.
Experimental studies suggest that bone fractures result in the release of cytokines and cells that might promote metastasis. Obtaining observational data on bone fractures after breast cancer diagnoses related to distant breast cancer recurrence could help to provide first epidemiological evidence for a metastasis-promoting effect of bone fractures. We used data from the largest German statutory health insurance fund (Techniker Krankenkasse, Hamburg, Germany) in a population-based cohort study of breast cancer patients with ICD-10 C50 codes documented between January 2015 and November 2019. The risk of metastasis overall, regional, distant non-bone or bone metastasis related to a fracture was modeled by an adjusted discrete time-to-event analysis with time-dependent exposure. Of 154,000 breast cancer patients, 84,300 fulfilled the inclusion criteria and had a follow-up time of more than half a year. During follow-up, fractures were diagnosed in 13,579 (16.1%) patients. Metastases occurred in 7047 (8.4%) patients; thereof 1544 had affected regional lymph nodes only and 5503 distant metastases. Fractures demonstrated a statistically significant association with subsequent metastasis overall (adjusted HR 1.12, 95% CI 1.04, 1.20). The highest risk for metastasis was observed in patients with subsequent bone metastasis (adjusted HR 1.18, 95% CI 1.05, 1.34), followed by distant non-bone metastasis (adjusted HR 1.16, 95% CI 1.07, 1.26) and lymph node metastasis (adjusted HR 1.08, 95% CI 0.97, 1.21).


Reference interval, longitudinal variability and reliability of activated clotting time in healthy dogs using a point-of-care analyser.
Activated clotting times (ACTs) are used to screen for coagulopathies and monitor heparin therapy. To determine a reference interval (RI) for ACT in dogs using a point-of-care analyser, to quantify intra-subject within- and between-day variability, to quantify analyser reliability and inter-analyser agreement and to study the influence of a delay in measurement. Forty-two healthy dogs were included. Measurements were performed on fresh venous blood using the i-STAT 1 analyser. The RI was determined using the Robust method. Intra-subject within-day variability and between-day variability were quantified between baseline and 2 h (n = 8) or 48 h (n = 10) later. Analyser reliability and inter-analyser agreement were studied by duplicate measurements (n = 8) on identical analysers. The influence of measurement delay was studied before and after a delay of one analytical run (n = 6). Mean, lower and upper reference limits for ACT were 92.9 ± 9.1, 74.4 and 111.2 s, respectively. Coefficients of variation of intra-subject within- and between-day variability were 8.1% and 10.4%, respectively, resulting in a significant between-day measurement difference. Analyser reliability assessed by the intraclass correlation coefficient and coefficient of variation were 0.87% and 3.3%, respectively. Significantly lower ACT values were observed after a measurement delay compared to direct analysis. Our study provides an RI for ACT in healthy dogs using the i-STAT 1 and suggests low intra-subject within- and between-day variability. Analyser reliability and inter-analyser agreement were good; however, analysis delay and between-day differences could significantly influence ACT results.


Mesenchymal stem cells promote pancreatic β-cell regeneration through downregulation of FoxO1 pathway.
Mesenchymal stem cells (MSC) are non-haematopoietic, fibroblast-like multipotent stromal cells. In the injured pancreas, these cells are assumed to secrete growth factors and immunomodulatory molecules, which facilitate the regeneration of pre-existing β-cells. However, when MSC are delivered intravenously, their majority is entrapped in the lungs and does not reach the pancreas. Therefore, the aim of this investigation was to compare the regenerative support of hTERT-MSC (human telomerase reverse transcriptase mesenchymal stem cells) via intrapancreatic (IPR) and intravenous route (IVR). hTERT-MSC were administered by IPR and IVR to 50% pancreatectomized NMRI nude mice. After eight days, blood glucose level, body weight, and residual pancreatic weight were measured. Proliferating pancreatic β-cells were labelled and identified with bromodeoxyuridine (BrdU) in vivo. The number of residual islets and the frequency of proliferating β-cells were compared in different groups with sequential pancreatic sections. The pancreatic insulin content was evaluated by enzyme-linked immunosorbent assay (ELISA) and the presence of hTERT-MSC with human Alu sequence. Murine gene expression of growth factors, β-cell specific molecules and proinflammatory cytokines were inspected by real-time polymerase chain reaction (RT-PCR) and Western blot. This study evaluated the regenerative potential of the murine pancreas post-hTERT-MSC administration through the intrapancreatic (IPR) and intravenous route (IVR). Both routes of hTERT-MSC transplantation (IVR and IPR) increased the incorporation of BrdU by pancreatic β-cells compared to control. MSC induced epidermal growth factor (EGF) expression and inhibited proinflammatory cytokines (IFN-γ and TNF-α). FOXA2 and PDX-1 characteristics for pancreatic progenitor cells were activated via AKT/ PDX-1/ FoxO1 signalling pathway. The infusion of hTERT-MSC after partial pancreatectomy (Px) through the IVR and IPR facilitated the proliferation of autochthonous pancreatic β-cells and provided evidence for a regenerative influence of MSC on the endocrine pancreas. Moderate benefit of IPR over IVR was observed which could be a new treatment option for preventing diabetes mellitus after pancreas surgery.


Kinetics of maternally acquired anti-hepatitis A antibodies: prediction of waning based on maternal or cord blood antibody levels.
Timing is critical for efficient hepatitis A vaccination in high endemic areas as high levels of maternal IgG antibodies against the hepatitis A virus (HAV) present in the first year of life may impede the vaccine response. To describe the kinetics of the decline of anti-HAV maternal antibodies, and to estimate the time of complete loss of maternal antibodies in infants in León, Nicaragua, a region in which almost all mothers are anti-HAV seropositive. We collected cord blood samples from 99 healthy newborns together with 49 corresponding maternal blood samples, as well as further blood samples at 2 and 7 months of age. Anti-HAV IgG antibody levels were measured by enzyme immunoassay (EIA). We predicted the time when antibodies would fall below 10 mIU/ml, the presumed lowest level of seroprotection. Seroprevalence was 100% at birth (GMC 8392 mIU/ml); maternal and cord blood antibody concentrations were similar. The maternal antibody levels of the infants decreased exponentially with age and the half-life of the maternal antibody was estimated to be 40 days. The relationship between the antibody concentration at birth and time until full waning was described as: critical age (months)=3.355+1.969 × log(10)(Ab-level at birth). The survival model estimated that loss of passive immunity will have occurred in 95% of infants by the age of 13.2 months. Complete waning of maternal anti-HAV antibodies may take until early in the second year of life. The here-derived formula relating maternal or cord blood antibody concentrations to the age at which passive immunity is lost may be used to determine the optimal age of childhood HAV vaccination.


Neuroinhibitory meroterpenoid compounds from Cordia oncocalyx.
Five new meroterpenoid compounds designed as rel-10β,11β-epoxy-2,11-dimethoxy-8α-hydroxy-8aβ-methyl-5α,6,7,8,8a,9,10,10aβ-octahydro-1,4-anthracendione (1), rel-10β,11β-epoxy-8α,5-dihydroxy-2-methoxy-8aβ-methyl-5,6,7,8,8a,9,10,10aβ-octahydro -1.4-anthracendione (2), rel-1,4,8α-trihydroxy-5-furanyl-2-methoxy-8aβ-methyl-6,7,8, 8a,9,10-hexahydro-10-anthracenone (3), rel-10α,11α-epoxy-8α,11β-dihydroxy-8aβ-methyl-5β,6,7,8,8a,9,10,10aβ-octahydro-1,4-anthracenediol (4) and rel-1,4,8α-trihydroxy-5-carboxyethyl-2-methoxy-8aβ-methyl-6,7,8,8a,9,10-hexahydro-10-anthra-cenone (5), besides seven (6-12) known compounds were isolated from the heartwood and sapwood ethanol extracts of Cordia oncocalyx. Moreover, the main isolated compounds were screened using the electrically driven mice vas deferens bioassay, which has a rich pharmacological receptors diversity.


Influence of depression on survival of colorectal cancer patients drawn from a large prospective cohort.
The prevalence of depressive symptoms immediately after the diagnosis of colorectal cancer (CRC) is high and has important implications both psychologically and on the course of the disease. The aim of this study is to analyse the association between depressive symptoms and CRC survival at 5 years after diagnosis. This multicentre, prospective, observational cohort study was conducted on a sample of 2602 patients with CRC who completed the Hospital Anxiety and Depression Scale (HADS-D) at 5 years of follow-up. Survival was analysed using the Kaplan-Meier method and Cox regression models. According to our analysis, the prevalence of depressive symptoms after a CRC diagnosis was 23.8%. The Cox regression analysis identified depression as an independent risk factor for survival (HR = 1.47; 95% CI: 1.21-1.8), a finding which persisted after adjusting for sex (female: HR = 0.63; 95% CI: 0.51-0.76), age (>70 years: HR = 3.78; 95% CI: 1.94-7.36), need for help (yes: HR = 1.43; 95% CI: 1.17-1.74), provision of social assistance (yes: HR = 1.46; 95% CI: 1.16-1.82), tumour size (T3-T4: HR = 1.56; 95% CI: 1.22-1.99), nodule staging (N1-N2: HR = 2.46; 95% CI: 2.04-2.96), and diagnosis during a screening test (yes: HR = 0.71; 95% CI: 0.55-0.91). There is a high prevalence of depressive symptoms in patients diagnosed with CRC. These symptoms were negatively associated with the survival rate independently of other clinical variables. Therefore, patients diagnosed with CRC should be screened for depressive symptoms to ensure appropriate treatment can be provided.


Characterization of iPSCs derived from dermal fibroblasts from a healthy 19year old female.
Primary fibroblasts from a healthy 19years old female were reprogrammed by transduction of retroviruses OCT4, SOX2, c-MYC and KLF4. iPSCs were characterized by immunocytochemistry, embryonic body-formation, DNA-fingerprint and karyotype analysis and comparative transcriptome analyses with the human embryonic stem cell line H1 revealed a Pearsons correlation coefficient of 0.8952.


A comprehensive mechanistic model for simulating algal-bacterial growth dynamics in photobioreactors.
A comprehensive mechanistic model with state of the art understanding and assumptions is presented to simulate major processes in a photobioreactor for describing the algal-bacterial growth dynamics. The model includes a total of 37 state variables that broadly cover all the essential physiological and physico-chemical processes in such a system. Model parameters are first calibrated with batch experimental data, and thereafter, extensive validation of the model is carried with long term independent experimental data in diverse conditions. The developed model is able to capture the complex system behavior with reasonable accuracy. Also, the comprehensive mathematical formulation with realistic assumptions make this model a valuable tool for gaining better insights into the complex system behavior.


Mist1 is necessary for the establishment of granule organization in serous exocrine cells of the gastrointestinal tract.
Establishing a pool of granules at the luminal border is a key step during exocrine cell development in the pancreas and is necessary for efficient release of digestive enzymes through regulated exocytosis. Several proteins have been linked to maintaining granule organization, but it is unclear which regulatory mechanisms are necessary to establish organization. Based on temporal and spatial expression, the transcription factor Mist1 is an excellent candidate, and analysis of mice that do not express Mist1 (Mist1KO) reveal disrupted cell morphology in adult pancreatic acini. To address Mist1's role in establishing granule location, we have characterized the organization of pancreatic acini throughout development in Mist1KO mice. Using various histological approaches, we have determined that correct granule organization is never established in pancreatic acini of Mist1KO mice. Further examination indicates that this disruption in granule targeting may be the primary defect in Mist1KO mice as granule organization is affected in other serous exocrine cells that normally express Mist1. To identify a mechanistic link between granule targeting and the loss of Mist1 function, intercellular junctions and the expression of Rab3D were assessed. While both of these factors are affected in Mist1KO mice, these changes alone do not account for the disorganization observed in Mist1KO tissues. Therefore, we conclude that Mist1 is necessary for complete differentiation and maturation of serous exocrine cells through the combined regulation of several exocrine specific genes.


Incremental binocular amplitude of the pattern visual evoked potential during the first five months of life: electrophysiological evidence of the development of binocularity.
The amplitude of the pattern visual evoked potential (VEP) of a binocular stimulus has been shown to be generally larger than the VEP obtained monocularly. There is evidence that this effect can be considered an electrophysiological index of fusion. To study how binocular vision develops in infancy we evaluated the incremental binocular amplitude (IBA) in three infants in a longitudinal investigation during the first five months of life. The stimuli were phase-alternating square-wave gratings with spatial and temporal parameters chosen to be appropriate for neonates. IBA was defined as the percentage increment of the largest binocular response compared with the monocular response. In the first two months of life IBA values were near zero, that is, no summation occurred. Between the second and third month IBA values rose markedly and after the third month its value was greater than 100%, demonstrating binocular facilitation. Thus in the first two months of life the eyes do not seem to cooperate as in adults. By the second and third month the binocular pattern VEP reflects an increasing binocular interaction. Other studies of the development of stereopsis have also found evidence of binocularity at similar ages.


Physician perspectives on the DNR order in Turkey: A survey of physicians in Internal Medicine.
Do not resuscitate (DNR) is a controversial ethico-legal issue and there is no legal regulation in Turkey. Evaluating the physicians' views on DNR is critical to the current problems and contributes to legal regulation. To examine the views of intensive care unit residents on DNR and the sociocultural and occupational factors affecting them. The research is a descriptive cross-sectional study. The sample of the study consists of 203 residents of internal medicine working in the intensive care unit in a university hospital. A questionnaire form was used as a data collection tool. 62.6% of the physicians know that there is no legal regulation regarding DNR in Turkey, and 14.3% think that DNR is performed. Female physicians approve of DNR at a higher rate than men (p<0.01). Physicians with more experience in the profession stated that not all patients should be performed cardiopulmonary resuscitation (p<0.01), and DNR should be a right (p<0.05). The vast majority of physicians stated that DNR should be legal (88.1%) and should be included in residency training (85.6%). It is necessary to establish legal regulations on DNR and implement residency training programs that will ensure the continuous professional development of physicians.


A compact hybrid-multiplexed potentiostat for real-time electrochemical biosensing applications.
The architecture and design of a compact, multichannel, hybrid-multiplexed potentiostat for performing electrochemical measurements on continuously-biased electrode arrays is presented. The proposed architecture utilises a combination of sequential and parallel measurements, to enable high performance whilst keeping the system low-cost and compact. The accuracy of the signal readout is maintained by following a special multiplexing approach, which ensures the continuous biasing of all the working electrodes of an array. After sampling the results, a digital calibration technique factors out errors from component inaccuracies. A prototype printed circuit board (PCB) was designed and built using off-the-shelf components for the real-time measurement of the amperometric signal of 48 electrodes. The operation and performance of the PCB was evaluated and characterised through a wide range of testing conditions, where it exhibited high linearity (R(2)>0.999) and a resolution of 400pA. The effectiveness of the proposed multiplexing scheme is demonstrated through electrochemical tests using KCl and [Fe(CN)6](3-) in KCl solutions. The applicability of the prototype multichannel potentiostat is also demonstrated using real biosensors, which were applied to the detection of IgA antibodies.


[The risk and treatment of hyperlipoproteinemias].
The role of lipid disorders in the pathogenesis of coronary heart disease is reviewed. It is also presented the pathophysiology of hyperlipidemias and its current therapeutic policies.


Evaluating the impact of methionine-enriched diets in the liver of European seabass through label-free shotgun proteomics.
Plant protein sources play an essential role in aquaculture by reducing the use of fish meal to sustainable levels, although further supplementation is needed to fulfill fish nutritional requirements. This work addressed fish growth performance and proteome changes to dietary methionine in European seabass juveniles. A dose-dependent response to methionine (Met) was observed on fish growth consistent with proteomic analyses, suggesting Met requirement ≥0.9% (w/w). Fish fed at 0.77% (w/w) exhibited reduced growth and an enrichment in proteins involved in cellular homeostasis. Proteomics data suggest an optimal nutritional status at 1.36% Met (w/w), together with putative beneficial effects on the immune system up to 1.66% Met (w/w). The response to dietary Met involved the convergence of different metabolic and signalling pathways implicated in cell growth and immune response e.g., mTOR, Hedgehog or the T Cell receptor signalling, coupled with a fine-tuning regulation of amino acid metabolism and translation.


Acute effects of cardiac contractility modulation on human induced pluripotent stem cell-derived cardiomyocytes.
Cardiac contractility modulation (CCM) is an intracardiac therapy whereby nonexcitatory electrical simulations are delivered during the absolute refractory period of the cardiac cycle. We previously evaluated the effects of CCM in isolated adult rabbit ventricular cardiomyocytes and found a transient increase in calcium and contractility. In the present study, we sought to extend these results to human cardiomyocytes using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to develop a robust model to evaluate CCM in vitro. HiPSC-CMs (iCell Cardiomyocytes2 , Fujifilm Cellular Dynamic, Inc.) were studied in monolayer format plated on flexible substrate. Contractility, calcium handling, and electrophysiology were evaluated by fluorescence- and video-based analysis (CellOPTIQ, Clyde Biosciences). CCM pulses were applied using an A-M Systems 4100 pulse generator. Robust hiPSC-CMs response was observed at 14 V/cm (64 mA) for pacing and 28 V/cm (128 mA, phase amplitude) for CCM. Under these conditions, hiPSC-CMs displayed enhanced contractile properties including increased contraction amplitude and faster contraction kinetics. Likewise, calcium transient amplitude increased, and calcium kinetics were faster. Furthermore, electrophysiological properties were altered resulting in shortened action potential duration (APD). The observed effects subsided when the CCM stimulation was stopped. CCM-induced increase in hiPSC-CMs contractility was significantly more pronounced when extracellular calcium concentration was lowered from 2 mM to 0.5 mM. This study provides a comprehensive characterization of CCM effects on hiPSC-CMs. These data represent the first study of CCM in hiPSC-CMs and provide an in vitro model to assess physiologically relevant mechanisms and evaluate safety and effectiveness of future cardiac electrophysiology medical devices.


Evaluation of AFP glycosylation heterogeneity in cancer patients with AFP-producing tumors.
It has been postulated that analysis of alpha-fetoprotein (AFP) glycosylation heterogeneity in cancer patients whose AFP levels are elevated (e.g., non-seminomatous germ cell tumors, ovarian germ cell tumors and primary hepatocellular carcinoma) might provide useful clinical information. We undertook a study to determine whether scrutiny of AFP glycosylation heterogeneity in patients with non-seminomatous germ cell tumors would provide information useful in diagnosis, staging, prognosis, or monitoring for recurrence of disease following therapy. While an analysis of AFP glycosylation heterogeneity using Concanavalin A lectin chromatography did not provide useful information in regard to staging or prognosis, it does supply unique information useful in discriminating between benign liver dysfunction (e.g. alcoholic hepatitis, chemotherapy-related liver damage) and that due to nonsemininomatous germ cell tumors. It was also concluded that an analysis of Concanavalin A binding patterns is not sufficient to discriminate between recurrent non-seminomatous germ cell tumor and primary hepatocellular carcinoma in patients with elevated serum AFP.


[Living related liver transplantation].
Liver transplantation has become established as a standard procedure in the treatment of end-stage liver diseases. Despite intense efforts by all parties involved up to the amendment of the German Transplantation Act, the lack of suitable donor organs was still one of the limiting factors of this therapeutic procedure. One way out of this problem is to make so-called marginal organs usable, e.g. with the help of machine perfusion or by utilizing living liver donation, which are used in some countries for more than 90% of organ donations. In general, there is no difference in the indications for liver transplantation between a (partial) organ obtained by post-mortem or living donation. Before any living donation, a thorough evaluation of the donor is carried out in order to minimize postoperative morbidity as far as possible. Technically the partial liver donation is based on the oncological liver resection, while the partial liver transplantation is a further development of split liver transplantation after post-mortem liver donation. In specialized centers comparable or even better results can nowadays be achieved using living liver donation instead of post-mortem donation.


Sensory Over-responsivity and Aberrant Plasticity in Cerebellar Cortex in a Mouse Model of Syndromic Autism.
Patients with autism spectrum disorder often show altered responses to sensory stimuli as well as motor deficits, including an impairment of delay eyeblink conditioning, which involves integration of sensory signals in the cerebellum. Here, we identify abnormalities in parallel fiber (PF) and climbing fiber (CF) signaling in the mouse cerebellar cortex that may contribute to these pathologies. We used a mouse model for the human 15q11-13 duplication (patDp/+) and studied responses to sensory stimuli in Purkinje cells from awake mice using two-photon imaging of GCaMP6f signals. Moreover, we examined synaptic transmission and plasticity using in vitro electrophysiological, immunohistochemical, and confocal microscopic techniques. We found that spontaneous and sensory-evoked CF-calcium transients are enhanced in patDp/+ Purkinje cells, and aversive movements are more severe across sensory modalities. We observed increased expression of the synaptic organizer NRXN1 at CF synapses and ectopic spread of these synapses to fine dendrites. CF-excitatory postsynaptic currents recorded from Purkinje cells are enlarged in patDp/+ mice, while responses to PF stimulation are reduced. Confocal measurements show reduced PF+CF-evoked spine calcium transients, a key trigger for PF long-term depression, one of several plasticity types required for eyeblink conditioning learning. Long-term depression is impaired in patDp/+ mice but is rescued on pharmacological enhancement of calcium signaling. Our findings suggest that this genetic abnormality causes a pathological inflation of CF signaling, possibly resulting from enhanced NRXN1 expression, with consequences for the representation of sensory stimuli by the CF input and for PF synaptic organization and plasticity.


[Animal experiments on particulars of the time factor in the development and solving of pulmonary atelectasis caused by foreign body (author's transl)].
In literature are only older publications about the temporal beginning of the acute atelectasis after obstructive foreign body occlusion of the bronchial system which are operated at the open thorax. For this reason experiments on animals were made to find out the earliest beginning of an atelectasis by a simple bronchial occlusion as an imitation of a natural process of a foreign body aspiration. The alterations in each single phase of development showed regularly based on serial radiographies and by the autopsy macroscopic and microscopic that about 2 or 3 h after aspiration of an obstructive foreign body it will be reckoned with a complete atelectasis. Only now correlate the clinical result, the X-ray and the pathological-anatomical alterations. The histological picture of the complete atelectasis follows the macroscopic result only in longer temporal distance. Atelectasis occuring before the mentioned moment cannot be explained by an absorption of air from the alveolar tissue, but they depend on foreign body independent reflexes (= reflex contraction atelectasis). In other series of experiments the retroplasia of an atelectasis showed no regularity after the release of the bronchial occlusion, as the time of development, but it is possible to say that it takes more time of retroplasia the longer the atelectasis lasts. Dependent on that the respiratory exchange was jerky into the atelectatic lung after a resting period without prefering any lobes of lungs where localised atelectatic foci remain a longer time.


Dual-Color Fluorescence Imaging of Magnetic Nanoparticles in Live Cancer Cells Using Conjugated Polymer Probes.
Rapid growth in biological applications of nanomaterials brings about pressing needs for exploring nanomaterial-cell interactions. Cationic blue-emissive and anionic green-emissive conjugated polymers are applied as dual-color fluorescence probes to the surface of negatively charged magnetic nanoparticles through sequentially electrostatic adsorption. These conjugated polymers have large extinction coefficients and high fluorescence quantum yield (82% for PFN and 62% for ThPFS). Thereby, one can visualize trace amount (2.7 μg/mL) of fluorescence-labeled nanoparticles within cancer cells by confocal laser scanning microscopy. Fluorescence labeling by the conjugated polymers is also validated for quantitative determination of the internalized nanoparticles in each individual cell by flow cytometry analysis. Extensive overlap of blue and green fluorescence signals in the cytoplasm indicates that both conjugated polymer probes tightly bind to the surface of the nanoparticles during cellular internalization. The highly charged and fluorescence-labeled nanoparticles non-specifically bind to the cell membranes, followed by cellular uptake through endocytosis. The nanoparticles form aggregates inside endosomes, which yields a punctuated staining pattern. Cellular internalization of the nanoparticles is dependent on the dosage and time. Uptake efficiency can be enhanced three-fold by application of an external magnetic field. The nanoparticles are low cytotoxicity and suitable for simultaneously noninvasive fluorescence and magnetic resonance imaging application.


Further insights into the role of angiotensin II in kidney development.
Over the past decade, compelling studies have highlighted the fundamental role of the renin-angiotensin system (RAS) in renal development and long-term control of renal function and arterial pressure. The present review provides an update of the understanding of how the RAS controls nephrogenesis and nephrovascular development. In addition, the investigations linking the perinatal development of RAS inhibition-induced renal dysmorphology and establishment of adult blood pressure are discussed.


Clinical and molecular profile of a new series of patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome: inconsistent correlation between forkhead box protein 3 expression and disease severity.
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is an autoimmune genetic disorder caused by mutation of the forkhead box protein 3 gene (FOXP3), a key regulator of immune tolerance. We sought to provide clinical and molecular indicators that facilitate the understanding and diagnosis of IPEX syndrome. In 14 unrelated affected male subjects who were given diagnoses of IPEX syndrome based on FOXP3 gene sequencing, we determined whether particular FOXP3 mutations affected FOXP3 protein expression and correlated the molecular and clinical data. Molecular analysis of FOXP3 in the 14 subjects revealed 13 missense and splice-site mutations, including 7 novel mutations. Enteropathy, generally associated with endocrinopathy and eczema, was reported in all patients, particularly in those carrying mutations within FOXP3 functional domains or mutations that altered protein expression. However, similar genotypes did not always result in similar phenotypes in terms of disease presentation and severity. In addition, FOXP3 protein expression did not correlate with disease severity. Severe autoimmune enteropathy, which is often associated with increased IgE levels and eosinophilia, is the most prominent early manifestation of IPEX syndrome. Nevertheless, the disease course is variable and somewhat unpredictable. Therefore genetic analysis of FOXP3 should always be performed to ensure an accurate diagnosis, and FOXP3 protein expression analysis should not be the only diagnostic tool for IPEX syndrome.


Intravenous sedation and patient response to minor oral surgery--experience of 408 cases.
This article presents the results of a patient questionnaire on response to minor oral surgery carried out under local anaesthetic and intravenous sedation. The predominantly favourable response of the respondents leads the author to suggest the use of IV sedation as a means of reducing patient anxiety, and so increasing dental attendance.


Outcome assessment in cardiovascular cost-benefit studies.
The scarcity of health resources and development of new treatments have introduced a need to assess health care interventions in the areas of both costs and benefits. Information on costs and benefits of one treatment program relative to another can assist decisions about resource allocation by indicating which interventions offer the greatest benefit at the least cost. Economic evaluation is dependent on accurate definition and appropriate measurement of outcome or benefit. This article reviews a number of evaluation techniques and cost-benefit studies associated with cardiovascular medicine. The focus is on health-related quality of life, the methodology, and the problems encountered therein. Methods for combining quantity and quality of life are discussed with reference to a composite measure of health outcome, quality-adjusted life years.


Ligand-induced structural transitions combined with paramagnetic ions facilitate unambiguous NMR assignments of methyl groups in large proteins.
NMR spectroscopy allows the study of biomolecules in close-to-native conditions. Structural information can be inferred from the NMR spectra when an assignment is available. Protein assignment is usually a time-consuming task, being specially challenging in the case of large, supramolecular systems. Here, we present an extension of existing state-of-the-art strategies for methyl group assignment that partially overcomes signal overlapping and other difficulties associated to isolated methyl groups. Our approach exploits the ability of proteins to populate two or more conformational states, allowing for unique NOE restraints in each protein conformer. The method is compatible with automated assignment algorithms, granting assignments beyond the limits of a single protein state. The approach also benefits from long-range structural restraints obtained from metal-induced pseudocontact shifts (PCS) and paramagnetic relaxation enhancements (PREs). We illustrate the method with the complete assignment of the 199 methyl groups of a MILproSVproSAT methyl-labeled sample of the UDP-glucose pyrophosphorylase enzyme from Leishmania major (LmUGP). Protozoan parasites of the genus Leishmania causes Leishmaniasis, a neglected disease affecting over 12 million people worldwide. LmUGP is responsible for the de novo biosynthesis of uridine diphosphate-glucose, a precursor in the biosynthesis of the dense surface glycocalyx involved in parasite survival and infectivity. NMR experiments with LmUGP and related enzymes have the potential to unravel new insights in the host resistance mechanisms used by Leishmania major. Our efforts will help in the development of selective and efficient drugs against Leishmania.


Enhanced antitumor activity of mitomycin C conjugated with anti-alpha-fetoprotein antibody by a novel method of conjugation.
Mitomycin C (MMC) was conjugated to horse anti-rat alpha-fetoprotein (AFP) antibody at the N-1a position through a glutaric acid-derived spacer arm. In vitro studies showed that MMC was spontaneously and slowly released from the conjugate. The conjugate caused a greater inhibition of both the in vitro and in vivo tumor growth of the AFP-producing rat hepatoma AH66 than did a mixture of anti-rat AFP antibody and MMC or a similar conjugate of MMC with normal horse immunoglobulin.


A case report of multicentric verrucous carcinoma of the female genital tract.
Verrucous carcinoma is a variant of squamous cell carcinoma with distinct features including slow locally invasive growth and verrucous appearance. Verrucous carcinoma of the vagina is considered an extremely rare lesion because only 17 cases have been reported in the literature. We report a case of vaginal verrucous carcinoma with a second focus in the cervix. The patient was treated with surgery and adjuvant interferon therapy for local recurrence. Human papillomavirus was detected in both vaginal and cervical tumor tissue by immunohistochemistry. Diagnosis of verrucous carcinoma may be difficult, particularly if biopsy specimen involves only the surface epithelium. The role of human papillomavirus as an etiologic agent in verrucous carcinoma is still a matter of discussion. Effective management requires surgical resection. The efficiencies of radiotherapy and interferon therapy are discussed.


A multi-disciplinary study of the ocular, orthopedic, and neurologic causes of abnormal head postures in children.
To determine the relative frequency that abnormal head postures in children are caused by orthopedic, ophthalmologic, or neurologic disorders, respectively. A prospective, consecutive case series. Children found to have an abnormal head posture on routine pediatric examination underwent an evaluation by a pediatric ophthalmologist, pediatric orthopedist, and pediatric neurologist. The study was conducted in northwestern Italy. In the 63 children evaluated, the cause of the abnormal head posture was orthopedic in 35, ocular in 25, and neurologic in 5. In 8 patients, no specific cause could be found. The most common orthopedic cause was congenital muscular torticollis, which accounted for 31 patients. The most common ocular cause was superior oblique muscle palsy, which accounted for 12 patients. In 2 patients neck muscle contracture suggested an orthopedic cause, however, the tight neck muscles were secondary to a head tilt caused by superior oblique muscle palsy. When the cause of an abnormal head posture is not obvious, a multi-disciplinary approach including ophthalmologic, neurologic, and orthopedic specialists may be helpful.


Ultra-low-dose spectral-detector computed tomography for the accurate quantification of pulmonary nodules: an anthropomorphic chest phantom study.
To assess the quantification accuracy of pulmonary nodules using virtual monoenergetic images (VMIs) derived from spectral-detector computed tomography (CT) under an ultra-low-dose scan protocol. A chest phantom consisting of 12 pulmonary nodules was scanned using spectral-detector CT at 100 kVp/10 mAs, 100 kVp/20 mAs, 120 kVp/10 mAs, and 120 kVp/30 mAs. Each scanning protocol was repeated three times. Each CT scan was reconstructed utilizing filtered back projection, hybrid iterative reconstruction, iterative model reconstruction (IMR), and VMIs of 40-100 keV. The signal-to-noise ratio and air noise of images, absolute differences, and absolute percentage measurement errors (APEs) of the diameter, density, and volume of the four scan protocols and ten reconstruction images were compared. With each fixed reconstruction image, the four scanning protocols exhibited no significant differences in APEs for diameter and density (all P > 0.05). Of the four scan protocols and ten reconstruction images, APEs for nodule volume had no significant differences (all P > 0.05). At 100 kVp/10 mAs, APEs for density using IMR were the lowest (APE-mean: 6.69), but no significant difference was detected between VMIs at 50 keV (APE-mean: 11.69) and IMR (P = 0.666). In the subgroup analysis, at 100 kVp/10 mAs, there were no significant differences between VMIs at 50 keV and IMR in diameter and density (all P > 0.05). The radiation dose at 100 kVp/10 mAs was reduced by 77.8% compared with that at 120 kVp/30 mAs. Compared with IMR, reconstruction at 100 kVp/10 mAs and 50 keV provides a more accurate quantification of pulmonary nodules, and the radiation dose is reduced by 77.8% compared with that at 120 kVp/30 mAs, demonstrating great potential for ultra-low-dose spectral-detector CT.


Nerve growth factor: an update on the science and therapy.
Nerve growth factor (NGF) is a key regulator of nociceptive pain and thus appears to be an interesting target molecule for an innovative class of analgesic medication. We set out to review the principles of neurogenic inflammation and results of anti-NGF regimens in animal studies as well as clinical trials with patients with back pain and osteoarthritis (OA). We searched using Google Scholar Search and Pubmed as well as through conference reports for articles and abstracts related to NGF and clinical trials using anti-NGF regimens. We report on efficacy findings and adverse events (AEs) related to these agents in this review. We identified five full articles and eight abstract reports relating to anti-NGF agents studied for use in back pain and in OA. Anti-NGF agents either alone or in combination with non-steroidal anti-inflammatory agents (NSAIDs) were more efficacious for the treatment of pain in a number of trials of knee and hip pain compared to NSAIDs alone. However, adverse effects that included rapidly progressive OA and joint replacement were more common in patients treated with anti-NGF and NSAIDs than either treatment alone. Anti-NGF treatment related neurologic symptoms including paresthesias, and potentially other types of adverse effects were usually transient but warrant additional investigation.


Germ cells of male mice express genes for peroxisomal metabolic pathways implicated in the regulation of spermatogenesis and the protection against oxidative stress.
Peroxisomes are organelles with main functions in the metabolism of lipids and of reactive oxygen species. Within the testis, they have different functional profiles depending on the cell types. A dysfunction of peroxisomes interferes with regular spermatogenesis and can lead to infertility due to spermatogenic arrest. However, so far only very little is known about the functions of peroxisomes in germ cells. We have therefore analyzed the peroxisomal compartment in germ cells and its alterations during spermatogenesis by fluorescence and electron microscopy as well as by expression profiling of peroxisome-related genes in purified cell populations isolated from mouse testis. We could show that peroxisomes are present in all germ cells of the germinal epithelium. During late spermiogenesis, the peroxisomes form large clusters that are segregated from the spermatozoa into the residual bodies upon release from the germinal epithelium. Germ cells express genes for proteins involved in numerous metabolic pathways of peroxisomes. Based on the expression profile, we conclude that newly identified functions of germ cell peroxisomes are the synthesis of plasmalogens as well as the metabolism of retinoids, polyunsaturated fatty acids and polyamines. Thus, germ cell peroxisomes are involved in the regulation of the homeostasis of signaling molecules regulating spermatogenesis and they contribute to the protection of germ cells against oxidative stress.


How Exciton Interactions Control Spin-Depolarization in Layered Hybrid Perovskites.
Using circularly polarized broadband transient absorption, time-resolved circular photoluminescence, and transient Faraday rotation spectroscopy, we report that spin-dependent interactions have a significant impact on exciton energies and spin depolarization times in layered Ruddlesden-Popper hybrid metal-halide perovskites. In BA2FAPb2I7, we report that room-temperature spin lifetimes are largest (3.2 ps) at a carrier density of ∼1017 cm-3 with increasing depolarization rates at higher exciton densities. This indicates that many-body interactions reduce spin-lifetimes and outcompete the effect of D'yakonov-Perel precessional relaxation that has been previously reported at lower carrier densities. We further observe a dynamic circular dichroism that arises from a photoinduced polarization in the exciton distribution between total angular momentum states. Our findings provide fundamental and application relevant insights into the spin-dependent exciton-exciton interactions in layered hybrid perovskites.


The long term results of mallet finger injury. A retrospective study of one hundred cases.
One hundred patients with mallet finger injuries were reviewed and examined three to five years after injury. Twenty nine patients still had symptoms consisting mainly of pain and cold intolerance. The degree of residual deformity, presence of a fracture, or delay in treatment were not related to symptoms.


Synthesis and Characterization of Zero-Valent Iron Nanoparticles, and the Study of Their Effect against the Degradation of DDT in Soil and Assessment of Their Toxicity against Collembola and Ostracods.
Of late, novel magnetic nanomaterials have drawn worldwide attention because of the uniqueness in their properties and uses. In our studies, we have prepared nearly monodisperse zero-valent iron nanoparticles (nZVIs) of diameter of less than 60 nm in aqueous medium by a reductive precipitation process and pectin as stabilizing agent. The characterization of these nanoparticles was done by dynamic light scattering and transmission electron microscopy (TEM) techniques. The TEM images confirmed that the average size of the nZVIs was about 25 nm. The resultant nZVIs were then employed to degrade DDT (dichlorodiphenyltrichloroethane) in spiked soil, and their toxicity toward Collembola (Folsomia candida) and Ostracods (Heterocypris incongruens) was measured. The fabricated nZVIs degraded DDT in soil quite effectively. Further, the effects of nZVIs on Collembola and Ostracods were found to be negative. This was due to the oxidation of nZVIs and creation of anoxic conditions thereupon, and the generation of excess Fe(II) in soil. In addition, the negative effects of DDT on ostracod development and Collembola reproduction were found to be quite weak.


Extended longevity of Caenorhabditis elegans by knocking in extra copies of hsp70F, a homolog of mot-2 (mortalin)/mthsp70/Grp75.
The Caenorhabditis elegans homolog of mortalin/mthsp70/Grp75 (called mot-2 hereafter) was isolated by screening of a nematode cDNA library with mouse mot-2 cDNA. The isolated clone matched to hsp70F of C. elegans. Analysis with two of the antibodies raised against hsp70F revealed that unlike mammalian mot-2, it is heat inducible. Transient induction of hsp70F by heat shock led to a slight (<13%) extension in the C. elegans life span. The transgenic worms that constitutively over-expressed hsp70F predominantly in muscle showed life span extension (approximately 43% for mean and approximately 45% for maximum life span) as compared to the wild-type and green fluorescent protein-transgenic worms. Life span extension of human cells was obtained by over-expression of mot-2 [Kaul et al. (2000) FEBS Lett. 474, 159-164]. Our results show, for the first time, that this member of the hsp70 family governs the longevity of worms and thus there are common pathways that determine mammalian and worm longevity.


Conformational similarity and systematic displacement of complementarity determining region loops in high resolution antibody x-ray structures.
Comparison of seven high resolution x-ray structures shows that the conformations of canonical complementarity determining region (CDR) loops, which are shared by these antibodies, are very similar. However, large spatial displacements (up to 2.7 A) of the essentially identical CDR loops become evident when the antibody beta-sheet frameworks, to which the loops are attached, are least-squares superposed. The loop displacements follow, and amplify, small positional differences in framework/loop splice points. Intradomain structural variability and, to a lesser extent, domain-domain orientation appear to cause the observed loop divergences. The results suggest that the selection of framework regions for loop grafting procedures is more critical than previously thought.


Modulus difference-induced embedding strategy to construct iontronic pressure sensor with high sensitivity and wide linear response range.
Sensitivity and linearity are two crucial indices to assess the sensing capability of pressure sensors; unfortunately, the two mutually exclusive parameters usually result in limited applications. Although a series of microengineering strategies including micropatterned, multilayered, and porous approach have been provided in detail, the conflict between the two parameters still continues. Here, we present an efficient strategy to resolve this contradiction via modulus difference-induced embedding deformation. Both the microscopic observation and finite element simulation results confirm the embedding deformation behavior ascribed to the elastic modulus difference between soft electrode and rigid microstructures. The iontronic pressure sensor with high sensitivity (35 kPa-1) and wide linear response range (0-250 kPa) is further fabricated and demonstrates the potential applications in monitoring of high-fidelity pulse waveforms and human motion. This work provides an alternative strategy to guide targeted design of all-around and comprehensive pressure sensor.