Suicide attempts and self-injurious behaviours in adolescent and adult patients with borderline personality disorder.
Prevalence data on self-mutilation and suicide attempts for adolescent borderline personality disorder (BPD) are currently not available. The purpose of this paper was to determine the frequency and methods of two forms of physically self-destructive acts (i.e. self-mutilation and suicide attempts) reported by adolescent borderline inpatients in one of the largest samples to date and to compare these results with a similarly diagnosed and assessed group of adult borderline inpatients. A total of 104 adolescent inpatients with BPD and 290 adult inpatients with BPD were interviewed about their lifetime history of physically self-destructive acts. The overall rates of self-mutilation (about 90%) and suicide attempts (about 75%) were similar during index admission for both adolescent and adult borderline patients. However, adolescents reported significantly higher rates of extreme levels of lifetime self-mutilation (e.g. >25 and >50 episodes) and cutting in particular, as compared with adult BPD. In contrast, borderline adults were significantly more likely to report a history of numerous (five or more) suicide attempts than adolescents with BPD. Self-mutilation and suicide attempts among adolescent borderline patients are prevalent and serious. Taken together, these results suggest that extreme levels of self-mutilation distinguish adolescent BPD from adults with BPD. Copyright © 2017 John Wiley & Sons, Ltd.


Number needed to treat estimates incorporating effects over the entire range of clinical outcomes: novel derivation method and application to thrombolytic therapy for acute stroke.
Number needed to treat (NNT) is a useful measure of a treatment's clinical benefit or harm. However, NNT estimates for treatments for neurologic conditions have previously been generated only for dichotomized functional outcomes, which may underestimate clinically relevant treatment effects. To develop a method for estimating NNTs for nonbinary outcomes from parallel design clinical trials and to illustrate its application to outcomes of fibrinolytic stroke therapy across the full range of the modified Rankin Scale (mRS) of disability. Expert generation of joint distribution outcome tables in a model population affords a novel means to derive NNTs for nonbinary end points. Using mRS distributions from the National Institute of Neurological Disorders and Stroke-Tissue Plasminogen Activator trials, 10 neurologist and emergency physician acute stroke care experts independently specified the joint distribution of outcomes in model samples of 100 patients assigned to placebo and active therapy. The average estimated NNT for 1 additional patient to have a better outcome by 1 or more grades on the mRS as a result of treatment was 3.1 (95% confidence interval, 2.6-3.6). The estimated number needed to harm was 30.1 (95% confidence interval, 25.1-36.0). Expert estimates were robust across alternative stratifications of the mRS, with the NNT for benefit on 6- and 5-rank versions of 3.3 and 3.7 and the number needed to harm of 56.6 and 100.0, respectively. Expert generation of joint distribution outcome tables enables NNT estimation across a full spectrum of nonbinary outcomes. For every 100 patients with acute stroke treated with tissue plasminogen activator, approximately 32 have a better final outcome and 3 have a worse final outcome as a result of treatment.


Teaching spontaneous responses to a young child with Down syndrome.
Children with Down syndrome experience significant communication impairments, particularly in expressive language. Although receiving little attention in the literature, deficiencies in expressive language are likely to affect spontaneous communicative responses in children with Down syndrome. In this study, using a multiple baseline design across responses, we demonstrated the effectiveness of discrete trial instruction in establishing spontaneous responses in a preschooler with Down syndrome. Spontaneous responses generalised to a novel setting involving a novel person and novel materials. Implications for the use of behaviourally based interventions to address the social-communicative needs of children with Down syndrome are discussed.


[Association between mesenteric phlebosclerosis and Chinese herbal medicine intake].
Mesenteric phlebosclerosis (MP) is a relatively rare disease of the colon. An association between MP and Chinese herbal medicine intake has recently been recognized. In the present study, we investigated the association between MP and Chinese herbal medicine intake in 42 patients, including those reported in the literature as well as those treated by us. Approximately 90% patients treated by us reported a history of Chinese herbal medicine intake, particularly kamishoyosan, orengedokuto, and sanshishi (gardeniae fructus), the lattermost being consumed by the majority of patients as a crude herbal medicine. Several MP patients report a history of Chinese herbal medicine intake. Furthermore, symptoms are exacerbated in MP patients who continue to consume the medicine after onset. Interestingly, MP was reported to develop in a married couple who had consumed the same Chinese herbal medicine for a prolonged period. These findings suggest that the intake of Chinese herbal medicine, particularly sanshishi, is strongly associated with MP development.


Did the UK's public health shielding policy protect the clinically extremely vulnerable during the COVID-19 pandemic in Wales? Results of EVITE Immunity, a linked data retrospective study.
The UK shielding policy intended to protect people at the highest risk of harm from COVID-19 infection. We aimed to describe intervention effects in Wales at 1 year. Retrospective comparison of linked demographic and clinical data for cohorts comprising people identified for shielding from 23 March to 21 May 2020; and the rest of the population. Health records were extracted with event dates between 23 March 2020 and 22 March 2021 for the comparator cohort and from the date of inclusion until 1 year later for the shielded cohort. The shielded cohort included 117,415 people, with 3,086,385 in the comparator cohort. The largest clinical categories in the shielded cohort were severe respiratory condition (35.5%), immunosuppressive therapy (25.9%) and cancer (18.6%). People in the shielded cohort were more likely to be female, aged ≥50 years, living in relatively deprived areas, care home residents and frail. The proportion of people tested for COVID-19 was higher in the shielded cohort (odds ratio [OR] 1.616; 95% confidence interval [CI] 1.597-1.637), with lower positivity rate incident rate ratios 0.716 (95% CI 0.697-0.736). The known infection rate was higher in the shielded cohort (5.9% vs 5.7%). People in the shielded cohort were more likely to die (OR 3.683; 95% CI: 3.583-3.786), have a critical care admission (OR 3.339; 95% CI: 3.111-3.583), hospital emergency admission (OR 2.883; 95% CI: 2.837-2.930), emergency department attendance (OR 1.893; 95% CI: 1.867-1.919) and common mental disorder (OR 1.762; 95% CI: 1.735-1.789). Deaths and healthcare utilisation were higher amongst shielded people than the general population, as would be expected in the sicker population. Differences in testing rates, deprivation and pre-existing health are potential confounders; however, lack of clear impact on infection rates raises questions about the success of shielding and indicates that further research is required to fully evaluate this national policy intervention.


Evaluating trends in private equity ownership and impacts on health outcomes, costs, and quality: systematic review.
To review the evidence on trends and impacts of private equity (PE) ownership of healthcare operators. Systematic review. PubMed, Web of Science, Embase, Scopus, and SSRN. Empirical research studies of any design that evaluated PE owned healthcare operators. The main outcome measures were impact of PE ownership on health outcomes, costs to patients or payers, costs to operators, and quality. The secondary outcome measures were trends and prevalence of PE ownership of healthcare operators. Studies were classified as finding either beneficial, harmful, mixed, or neutral impacts of PE ownership on main outcome measures. Results across studies were narratively synthesized and reported. Risk of bias was evaluated using ROBINS-I (Risk Of Bias In Non-randomised Studies of Interventions). The electronic search identified 1778 studies, with 55 meeting the inclusion criteria. Studies spanned eight countries, with most (n=47) analyzing PE ownership of healthcare operators in the US. Nursing homes were the most commonly studied healthcare setting (n=17), followed by hospitals and dermatology settings (n=9 each); ophthalmology (n=7); multiple specialties or general physician groups (n=5); urology (n=4); gastroenterology and orthopedics (n=3 each); surgical centers, fertility, and obstetrics and gynecology (n=2 each); and anesthesia, hospice care, oral or maxillofacial surgery, otolaryngology, and plastics (n=1 each). Across the outcome measures, PE ownership was most consistently associated with increases in costs to patients or payers. Additionally, PE ownership was associated with mixed to harmful impacts on quality. These outcomes held in sensitivity analyses in which only studies with moderate risk of bias were included. Health outcomes showed both beneficial and harmful results, as did costs to operators, but the volume of studies for these outcomes was too low for conclusive interpretation. In some instances, PE ownership was associated with reduced nurse staffing levels or a shift towards lower nursing skill mix. No consistently beneficial impacts of PE ownership were identified. Trends in PE ownership rapidly increased across almost all healthcare settings studied. Such ownership is often associated with harmful impacts on costs to patients or payers and mixed to harmful impacts on quality. Owing to risk of bias and frequent geographic focus on the US, conclusions might not be generalizable internationally. PROSPERO CRD42022329857.


Effect of vertebroplasty with bone cement on osteoporotic compression fractures in elderly patients.
To explore the effect of vertebroplasty with bone cement on elderly patients with osteoporotic compression fractures. A retrospective study was conducted on 130 patients with osteoporotic compression fractures treated at the Second Hospital of Hebei Medical University from January 2018 to January 2022. According to different treatment methods, 50 patients who underwent conservative treatment were included in a control group (CG), and 80 patients who underwent vertebroplasty were included in a research group (RG). The anterior vertebral height, kyphotic Cobb angle, and Oswestry Disability Index (ODI) score in both groups were observed before and after treatment. The Visual Analogue Scale (VAS) scores were compared between the two groups before and after treatment. The quality of life and efficacy were evaluated in both groups. After treatment, the anterior vertebral height in the RG exhibited a significant increase compared to that before treatment, and both groups showed a significant decrease in the Cobb angle and ODI (P<0.05). Furthermore, the RG exhibited notably higher anterior vertebral height, and significantly lower Cobb angle and ODI than the CG after treatment (P<0.05). The post-treatment VAS score decreased significantly in both groups (P<0.05), and was lower in the RG than that in CG (P<0.05). After treatment, the quality of life scores improved significantly in both groups (P<0.05), but the RG demonstrated significantly higher scores in the role-emotional, physical functioning, social functioning, and general health (GH) dimensions compared to the CG (P<0.05). The total response rate in the CG was significantly lower than that in the RG (P<0.05). Age, course of disease, underlying disease, distribution of bone cement, and leakage of bone cement were found to be risk factors affecting the prognosis of patients. Logistic regression analysis showed that course of disease, distribution of bone cement, and leakage of bone cement were independent risk factors affecting prognosis. Vertebroplasty with bone cement is an effective treatment for elderly patients suffering from osteoporotic compression fractures. This intervention can improve anterior vertebral height, kyphotic Cobb angle, and ODI, while alleviating pain and enhancing the quality of life. Given its promising clinical outcomes, this treatment is highly recommended.


Efficacy of an 8-hour education intervention on dementia knowledge, attitude and skills in healthcare professionals in regional hospitals: a nation-wide study from Uganda.
dementia imposes an enormous burden, mainly in low-income countries (LICs). Due to lack of well-trained healthcare professionals, 70-90% of people with dementia do not receive adequate care in LICs. The aim of this study was to evaluate whether a one-day, 8-hour medical education intervention on dementia care improves the knowledge and attitude about and confidence in providing dementia care among healthcare professionals in 8 referral hospitals in UgandaMethods: in this pre-test/post-test study without a control group, participants completed the Alzheimer´s Disease Knowledge Scale (ADKS), Dementia Care Attitude Scale (DCAS), and 9 visual analogue scales (VAS) regarding confidence in specific dementia care skills pre- and post-medical education intervention. in one hundred twelve healthcare professionals (age = 41.7±10.2 years; 54.5% women), the ADKS, DCAS, and VAS scores for recognizing and assessing core dementia symptoms, communicating effectively, providing psycho-education, activating patients mentally and physically, managing behavioral and psychological symptoms, and involving carers in the treatment improved significantly (P < 0.001) post-medical education intervention. our study demonstrates that brief educational interventions are efficacious in strengthening the dementia literacy among healthcare professionals in a low-income country. Future research should explore whether such brief educational interventions also result in implementation of efficacious dementia care into routine clinical practice and whether it ultimately may lead to improved health outcomes in patients and formal and informal caregivers.


Description and early outcomes of the hybrid graft for dialysis.
Long-term dialysis access has become more challenging as patient survival has improved in end-stage renal disease. The GORE® Hybrid Vascular Graft (GHVG) has been designed to improve dialysis access outcomes and provide additional access options for challenging patients. In this article, we will review the design of the graft, unique properties and reported outcomes. We reviewed data available at our institution and performed a Pubmed search on GORE® Hybrid Vascular graft. We found two more studies besides the data published by our department. To date, there have been three papers showing early results of these grafts. All studies report successful placement of the grafts with no unexpected complications. Limb edema has not been a common problem, despite concerns of placing a stent graft into the axillary vein. The papers have shown 70% cumulative patency of the GHVG at 12 months. The comparative studies showed no significant benefit compared to conventional grafts. We see this as an option of continuing with arm access rather than going to more complex access creation such as a chest wall access or going to access creation in the legs. The GHVG has been shown to have comparable performance to standard arteriovenous graft techniques and can expand access options for some patients with challenging anatomy.


Intravenous thrombolysis pretreatment and other predictors of infarct in a new previously unaffected territory (INT) in ELVO strokes treated with mechanical thrombectomy.
One uncommon complication of mechanical thrombectomy (MT) is an infarct in a new previously unaffected territory (infarct in new territory (INT)). To evaluate the predictors of INT with special focus on intravenous thrombolysis(IVT)pretreatmentbefore MT. Consecutive patients with emergent large vessel occlusion (ELVO) treated with MT during a 5-year period were evaluated. INT was defined using standardized methodology proposed by ESCAPE investigators. The predictors of INT and its impact on outcomes were investigated. A total of 419 consecutive patients with ELVO received MT (mean age 64±15 years, 50% men, median baseline National Institutes of Health Stroke Scale score 16 points (IQR 11-20), 69% pretreated with IVT). The incidence of INT was lower in patients treated with combination therapy (IVTandMT) than in patients treated with MT alone, respectively (10% vs 20%; p=0.011). The INT group had more patients with posterior circulation occlusions than the group without INT (28% vs 10%, respectively; p<0.001). The rates of 3-month functional independence were lower in patients with INT (30% vs 50%; p=0.007). IVT pretreatment was not independently related to INT (OR=0.75; 95% CI 0.32 to 1.76), and INT did not emerge as an independent predictor of 3-month functional independence (OR=0.69; 95% CI 0.29 to 1.62) on multivariable logistic regression models. Location of posterior circulation occlusion was independently associated with a higher odds of INT (OR=3.33; 95% CI 1.43 to 7.69; p=0.005). IVT pretreatment is not independently associated with a lower likelihood of INT in patients with ELVO treated with MT. Patients with ELVO with posterior circulation occlusion are more likely to have INT after MT.


t-Darpp overexpression in HER2-positive breast cancer confers a survival advantage in lapatinib.
Drug resistance is a major barrier to successful cancer treatment. For patients with HER2-positive breast cancer who initially respond to therapy, the majority develop resistance within one year of treatment. Patient outcomes could improve significantly if we can find and exploit common mechanisms of acquired resistance to different targeted therapies. Overexpression of t-Darpp, a truncated form of the dual kinase/phosphatase inhibitor Darpp-32, has been linked to acquired resistance to trastuzumab, a front-line therapy for HER2-positive breast cancer. Darpp-32 reverses t-Darpp's effect on trastuzumab resistance. In this study, we examined whether t-Darpp could be involved in resistance to lapatinib, another HER2-targeted therapeutic. Lapatinib-resistant SKBR3 cells (SK/LapR) showed a marked change in the Darpp-32:t-Darpp ratio toward a predominance of t-Darpp. Overexpression of t-Darpp alone was not sufficient to confer lapatinib resistance, but cells that overexpress t-Darpp partially mimicked the molecular resistance phenotype observed in SK/LapR cells exposed to lapatinib. SK/LapR cells failed to down-regulate Survivin and failed to induce BIM accumulation in response to lapatinib; cells overexpressing t-Darpp exhibited only the failed BIM accumulation. t-Darpp knock-down reversed this phenotype. Using a fluorescence-based co-culture system, we found that cells overexpressing t-Darpp formed colonies in lapatinib within 3-4 weeks, whereas parental cells in the same co-culture did not. Overall, t-Darpp appears to mediate a survival advantage in lapatinib, possibly linked to failed lapatinib-induced BIM accumulation. t-Darpp might also be relevant to acquired resistance to other cancer drugs that rely on BIM accumulation to induce apoptosis.


Surgery versus thrombolysis for initial management of acute limb ischaemia.
Both peripheral arterial thrombolysis and surgery can be used in the management of peripheral arterial ischaemia. Much is known about the indications, risks, and benefits of thrombolysis. However, whether thrombolysis works better than surgery for initial management of acute limb ischaemia remains unknown. This is the second update of the review first published in 2002. To determine whether thrombolysis or surgery is the more effective technique in the initial management of acute limb ischaemia due to thromboembolism. For this update, the Cochrane Vascular Information Specialist (CIS) searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE Ovid, Embase Ovid, CINAHL, AMED, and clinical trials registries up to 7 May 2018. All randomised controlled studies comparing thrombolysis and surgery for initial treatment of acute limb ischaemia. We independently assessed trial quality and extracted data. Agreement was reached by consensus. We performed analyses using odds ratios (ORs) and 95% confidence intervals (CIs). We identified no new studies for this update. We included five trials with a total of 1292 participants; agents used for thrombolysis were recombinant tissue plasminogen activator and urokinase. Trials were generally of moderate methodological quality. The quality of evidence according to GRADE was generally low owing to risk of bias (lack of blinding), imprecision in estimates, and heterogeneity.Trial results showed no clear differences in limb salvage, amputation, or death at 30 days (odds ratio (OR) 1.02, 95% confidence interval (CI) 0.41 to 2.55, 4 studies, 636 participants; OR 0.97, 95% CI 0.51 to 1.85, 3 studies, 616 participants; OR 0.59, 95% CI 0.31 to 1.14, 4 studies, 636 participants, respectively), and we rated the evidence as low, low, and moderate quality, respectively. Trial results show no clear differences for any of the three outcomes at six months or one year between initial surgery and initial thrombolysis. A single study evaluated vessel patency, so no overall association could be determined (OR 0.46, 95% CI 0.08 to 2.76, 20 participants; very low-quality evidence). Evidence of increased risk of major haemorrhage (OR 3.22, 95% CI 1.79 to 5.78, 4 studies, 1070 participants; low-quality evidence) and distal embolisation (OR 31.68, 95% CI 6.23 to 161.07, 3 studies, 678 participants; very low-quality evidence) was associated with thrombolysis treatment at 30 days, and there was no clear difference in stroke (OR 5.33, 95% CI 0.95 to 30.11, 5 studies, 1180 participants; low-quality evidence). Participants treated by initial thrombolysis had a greater reduction in the level of intervention required, compared with a pre-intervention prediction, at 30 days (OR 9.06, 95% CI 4.95 to 16.56, 2 studies, 502 participants). None of the included studies evaluated time to thrombolysis as an outcome. There is currently no evidence in favour of either initial thrombolysis or initial surgery as the preferred option in terms of limb salvage, amputation, or death at 30 days, six months, or one year. Low-quality evidence suggests that thrombolysis may be associated with higher risk of haemorrhagic complications and ongoing limb ischaemia (distal embolisation). The higher risk of complications must be balanced against risks of surgery in each individual case. Trial results show no statistical difference in stroke, but the confidence interval is very wide, making it difficult to interpret whether this finding is clinically important. We used GRADE criteria to assess the quality of the evidence as generally low. We downgraded quality owing to risk of bias, imprecision, and heterogeneity between included studies.


Isolation and characterization of 30 STRs in Temminck's ground pangolin (Smutsia temminckii) and potential for cross amplification in other African species.
Temminck's ground pangolin (Smutsia temminckii) is one of four species of pangolin, endemic to Africa. Two of the African pangolin species are listed as vulnerable and two are listed as endangered on the International Union for Conservation of Nature Red List of Threatened Species due to their ongoing exploitation for traditional medicine and bushmeat. In this study, we developed 30 species-specific short-tandem repeats (STRs) in Temminck's ground pangolin using next-generation sequencing. The markers were also optimized for crossamplification in other African species. All the markers amplified successfully in Temminck's ground pangolin with allelic polymorphisms observed in 87% of the markers in giant pangolin (S. gigantea) whereas 60% of the markers were amplified polymorphic loci in both whitebellied pangolin (Phataginus tricuspis) and black-bellied pangolin (P. tetradactyla). Analysis of diversity estimates showed moderate levels of variability in Temminck's ground pangolin (Na = 5; Ho = 0.559), giant pangolin (Na = 4.909; Ho = 0.514) and white-bellied pangolin (Na= 2.686; Ho = 0.541) with lower values being observed in black-bellied pangolin (Na = 3; Ho = 0.242). This study provides data of the first available STR markers which was amplified in all four African pangolin species that can now be used in conservation genetic and evolutionary aspects of population histories.


A compositional segmentation of the human mitochondrial genome is related to heterogeneities in the guanine mutation rate.
We applied a hidden Markov model segmentation method to the human mitochondrial genome to identify patterns in the sequence, to compare these patterns to the gene structure of mtDNA and to see whether these patterns reveal additional characteristics important for our understanding of genome evolution, structure and function. Our analysis identified three segmentation categories based upon the sequence transition probabilities. Category 2 segments corresponded to the tRNA and rRNA genes, with a greater strand-symmetry in these segments. Category 1 and 3 segments covered the protein- coding genes and almost all of the non-coding D-loop. Compared to category 1, the mtDNA segments assigned to category 3 had much lower guanine abundance. A comparison to two independent databases of mitochondrial mutations and polymorphisms showed that the high substitution rate of guanine in human mtDNA is largest in the category 3 segments. Analysis of synonymous mutations showed the same pattern. This suggests that this heterogeneity in the mutation rate is partly independent of respiratory chain function and is a direct property of the genome sequence itself. This has important implications for our understanding of mtDNA evolution and its use as a 'molecular clock' to determine the rate of population and species divergence.


Incidence of chancroid in Vienna from 1980 to 1988.
The authors report on a retrospective study of the occurrence of chancroid in the city of Vienna during the past 10 years. After identifying two patients at the authors' department with chancroid in March 1988, the authors investigated the frequency with which this disease presented during the last 10 years. Of 32 patients, six presented between 1977 and 1980, and one patient in 1987. The remaining 25 patients were diagnosed within a 4-month period in 1981, suggesting a limited outbreak. The source of this infection could be traced to Turkey; infected prostitutes contributed to further spread in Vienna. All patients were treated successfully with sulfamethoxazole/trimethoprim. Efficient control of this outbreak can be attributed to inpatient treatment of the prostitutes. Appropriate and timely treatment must be preceeded by careful and exact diagnosis of this disease whose clinical picture is constantly diverging from its classical form.


PINK1/Parkin-mediated mitophagy in mechanical ventilation-induced diaphragmatic dysfunction.
Mechanical ventilation (MV) often leads to ventilation-induced diaphragm dysfunction (VIDD). Although the development of this disorder had been linked to oxidative stress, mitochondrial energy deficiency, autophagy activation, and apoptosis in the diaphragm, it remains unclear whether the activation of mitophagy can induce VIDD. With our research, our endeavor is to uncover whether PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy affects the MV-caused diaphragmatic dysfunction. Sprague-Dawley rats were subjected to MV treatment for 6 h (MV-6h), 12 h (MV-12h), or 24 h (MV-24h). Post MV, the diaphragm muscle compound action potential (CMAP) and cross-sectional areas (CSAs) of the diaphragm of these rats were measured. The levels of proteins of interest were examined to assess muscle health, mitochondrial dynamics, and mitophagy in the diaphragm. The co-localization of PINK1 with the mitochondrial protein marker tom20 was examined, as well as transmission electron microscopy analysis to detect changes in diaphragm mitochondrial ultrastructure. MV-12h and MV-24h treatments resulted in a decrease in CSA of diaphragm and CMAP amplitude. In addition, the expressions of F-box (MFAbx), muscle-specific ring finger 1 (MURF1), PINK1, and p62 were elevated in rats treated with MV for 12 h and 24 h, while mfn2 expression was reduced. Rats following MV-24h treatment displayed an increase in mitochondrial dynamic protein (Drp1) and Parkin expression and microtubule-associated protein 1 light chain 3/1 (LC3II/I) ratio. Moreover, decreased SOD and GSH activity and membrane potential were observed after MV-12h and MV-24h treatment, while H2O2 activity increased after MV-24h treatment. In addition, a strong co-localization between PINK1 and tom20 was identified. These results reveal that MV leads to various changes in mitochondrial dynamics and significantly increases the mitophagy levels, which subsequently cause the variation in diaphragmatic function and muscle atrophy, indicating that mitophagy could be one of the possible mechanisms by which MV induces diaphragmatic dysfunction.The reviews of this paper are available via the supplemental material section.


How do gravity alterations affect animal and human systems at a cellular/tissue level?
The present white paper concerns the indications and recommendations of the SciSpacE Science Community to make progress in filling the gaps of knowledge that prevent us from answering the question: "How Do Gravity Alterations Affect Animal and Human Systems at a Cellular/Tissue Level?" This is one of the five major scientific issues of the ESA roadmap "Biology in Space and Analogue Environments". Despite the many studies conducted so far on spaceflight adaptation mechanisms and related pathophysiological alterations observed in astronauts, we are not yet able to elaborate a synthetic integrated model of the many changes occurring at different system and functional levels. Consequently, it is difficult to develop credible models for predicting long-term consequences of human adaptation to the space environment, as well as to implement medical support plans for long-term missions and a strategy for preventing the possible health risks due to prolonged exposure to spaceflight beyond the low Earth orbit (LEO). The research activities suggested by the scientific community have the aim to overcome these problems by striving to connect biological and physiological aspects in a more holistic view of space adaptation effects.


Enabling N-to-C Ser/Thr Ligation for Convergent Protein Synthesis via Combining Chemical Ligation Approaches.
In this article, Ser/Thr ligation(on/off) has been realized to enable N-to-C successive peptide ligations using a salicylaldehyde semicarbazone (SAL(off)) group by in situ activation with pyruvic acid of the peptide SAL(off) ester into the peptide salicylaldehyde (SAL(on)) ester. In addition, a peptide with a C-terminal thioester and N-terminal Ser or Thr as the middle peptide segment can undergo one-pot Ser/Thr ligation and native chemical ligation in the N-to-C direction. The utility of this combined ligation strategy in the N-to-C direction has been showcased through the convergent assembly of a human cytokine protein sequence, GlcNAcylated interleukin-25.


The effect of a high-flex implant on postoperative flexion after primary total knee arthroplasty.
Compared to a statistically similar cohort, patients implanted with a high-flex poster-stabilized prosthesis achieved greater return of flexion than that with a standard posterior stabilized implant. In addition, patients with a high flexion arc preoperatively retained this high arc of flexion after surgery. Finally, there was an increase in the range of flexion seen after surgery in both groups of patients, but larger in the group in which the modified high-flexion implant was used.


[Russia-Halle interrelations in medicine of the 18th century. II. Halle medical delegations in Czar Peter's Russia and later].
In the 18th century for the purpose of amelioration of the medical care by the authorities responsible for the medicinal organization in Russia aimed methods of delegation were brought about. Requests of such kind were sent to the medical faculties of renowned universities. In such requests the University of Halle played a significant role. For the 18th century more than 40 candidates for a Halle doctorate can be authenticated who took Russian services for a certain time or for ever and there obtained important positions during their stay.


Shock compression of quartz to 1.6 TPa: redefining a pressure standard.
Evaluation of models and theory of high-pressure material response is largely made through comparison with shock wave data, which rely on impedance match standards. The recent use of quartz as a shock wave standard has prompted a need for improved data. We report here on measurements of the quartz Hugoniot curve from 0.1-1.6 TPa. The new data, in agreement with our ab initio calculations, reveal substantial errors in the standard and have immediate ramifications for the equations of state of deuterium, helium, and carbon at pressures relevant to giant planets and other high-energy density conditions.


Combination of organotrifluoroborates with photoredox catalysis marking a new phase in organic radical chemistry.
Combination of organotrifluoroborates and visible-light-driven photoredox catalysis, both of which have attracted the attention of synthetic chemists, marks a new phase in the field of organic radical chemistry. We have developed photoredox-catalyzed radical reactions with organotrifluoroborates, which turn out to serve not only as a source of organic radicals but also as radical acceptors. The first part of this Perspective deals with the generation of organic radicals from organotrifluoroborates, and the latter part describes addition of the CF3 radical to alkenyltrifluoroborates. The good chemistry between organoborates and photoredox catalysis and its future will be discussed.


Paragonimiasis in Yongjia County, Zhejiang Province, China: clinical, parasitological and karyotypic studies on Paragonimus westermani.
Paragonimiasis in Yongjia County, Zhejiang Province, China, has been of such public health concern that a specialized Institute for Paragonimiasis Control has been established there. The study reported here involved both parasitological research on Paragonimus westermani in the endemic areas and a clinical analysis of 94 cases of paragonimiasis. Eggs were found in sputum, feces and brain tissue in 45 cases. Twenty patients, 19 of whom where children under 10 years of age, showed hepatic injury. Treatment with praziquantel or bithionol had satisfactory results in all cases. Dimensions of the parasite eggs, metacercariae from freshwater crabs and adult flukes suggested that the form of P. westermani in Yongjia is the 'small type': a suggestion supported by karyotypic studies on gonad cells from adult flukes collected from experimentally infected animals as all were found to be diploid. In conclusion, the 'small type' or diploid form of P. westermani is the cause of paragonimiasis pulmonary symptoms in Yongjia.


Who's minding the data? Data Monitoring Committees in clinical cancer trials.
Modern biomedicine is based on a number of novel institutions and practices that, in order to function, require some degree of formal and informal regulation. This paper contributes to the ongoing investigation of these processes, and the forms of objectivity they generate, by examining the emergence, development and deployment of Data Monitoring Committees in the field of clinical trials. The idea of a DMC had originally been raised in the clinical trial methodology literature in the 1970s so as to solve the problem of the management of interim trial data. Many leading clinical trial statisticians proposed that interim data and analyses be restricted to members of a DMC. Since the late 1980s, DMCs have evolved considerably in a constant search for ethical neutrality and objectivity through the use of sophisticated statistical techniques and novel organisational strategies. They have also been beset by a fundamental tension as to who or what should count as objective in such an undertaking. The paper examines the evolution of this institution in terms of the techniques brought to bear on the issues that they are expected to solve, the organisational forms through which DMCs have evolved and the ideals of objectivity that these forms embody.


Ex vivo perfusion of the swine heart as a method for pre-transplant assessment.
We describe a cost-effective, reproducible circuit in a porcine, ex vivo, continuous warm-blood, bi-ventricular, working heart model that has future possibilities for pre-transplant assessment of marginal hearts donated from brain stem dead donors and hearts donated after circulatory determination of death (DCDD). In five consecutive experiments over five days, pressure volume loops were performed. During working mode, the left ventricular end systolic pressure volume relationship (LV ESPVR) was 23.1±11.1 mmHg/ml and the LV preload recruitable stroke work (PRSW) was 67.8±7.2. (Standard PVAN analysis software) (Millar Instruments, Houston, TX, USA) All five hearts were perfused for 219±64 minutes and regained normal cardiac function on the perfusion system.They displayed a significant upward and leftward shift of the end systolic pressure volume relationship, a significant increase in preload recruitable stroke work and minimal stiffness. These hearts could potentially be considered for transplantation. The circuit was effective during reperfusion and working modes whilst proving to be successful in maintaining cardiac function in excess of four hours. Using an autologous prime of approximately 20% haematocrit (Hct), electrolytes and blood gases were easy to control within this period using standard perfusion techniques.


Plutonium and Americium Aluminate Perovskites.
Both AmAlO3 and PuAlO3 perovskites have been synthesized and characterized using powder X-ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR), and 27Al magic angle spinning nuclear magnetic resonance spectroscopy (MAS NMR). AmAlO3 perovskite showed a rhombohedral configuration (space group R3̅c) in agreement with previous studies. The effect of americium α-decay on this material has been followed by XRD and 27Al MAS NMR analyses. In a first step, a progressive increase in the level of disorder in the crystalline phase was detected, associated with a significant crystallographic swelling of the material. In a second step, the crystalline AmAlO3 perovskite was progressively converted into amorphous AmAlO3, with a total amorphization occurring after 8 months and 2 × 1018 α-decays/g. For the first time, PuAlO3 perovskite was synthesized with an orthorhombic configuration (space group Imma), showing an interesting parallel to CeAlO3 and PrAlO3 lanthanide analogues. High-temperature XRD was performed and showed a Imma → R3̅c phase transition occurring between 473 and 573 K. The thermal behavior of R3̅c PuAlO3 was followed from 573 to 1273 K, and extrapolation of the data suggests that cubic plutonium perovskite should become stable at around 1850 K (R3̅c → Pm3̅m transition).


Novel synthesis of (S)-1-[5-(benzoylamino)-1,4-dioxo-6-phenylhexyl]-L-proline and analogues: potent angiotensin converting enzyme inhibitors.
A new approach was developed for the synthesis of (S)-1-[5-(benzoylamino)-1,4-dioxo-6-phenylhexyl]-L-proline (1) and 23 analogues. The delta-(acylamino)-gamma-keto acid intermediates were obtained by a modified Dakin--West reaction using 3-carbomethoxypropionyl chloride. Acylation of L-proline and recrystallization of the mixture of diastereomers gave the optically pure title compound in three reaction steps. The in vitro angiotensin converting enzyme (ACE) inhibitory activity of 1 was confirmed. Some of the novel analogues (6, 11, 13, and 17) were also found to be potent inhibitors of ACE in vitro with an IC50 of 1.4-8.8 x 10(-9) M (IC50 for captopril = 0.9 x 10(-8) M). In vivo these compounds (6, 11, 17, and 18) were much less active than captopril, especially by the oral route. Against angiotensin I (AI) challenge in normotensive conscious rats, 1 and 6 produced less than 50% inhibition at 30 mg/kg po but 57 to 82% inhibition at 3 mg/kg iv. Inhibition by both routes lasted less than 1 h. In renal hypertensive rats, 1 and 15 of its analogues failed to produce significant blood pressure lowering effects, in contrast to the marked effects of captopril. Near maximum inhibition of AI was achieved by continuous intravenous infusions of 1 and 20, suggesting that limited oral activity may by due to degradation and/or clearance.


Molluscum contagiosum: the importance of early diagnosis and treatment.
Molluscum contagiosum is a viral infection that is becoming an increasing problem in sexually active individuals and in patients with human immunodeficiency virus. Although molluscum contagiosum lesions are generally self-limiting, it may take 6 months to 5 years for lesions to disappear. Furthermore, patients with weakened immune systems have increased difficulty in clearing lesions; therefore lesions typically persist for prolonged periods. Although there has been continued debate about whether molluscum contagiosum lesions should be treated or allowed to resolve spontaneously, many clinicians recommend treatment of genital molluscum contagiosum lesions to reduce the risk of sexual transmission, prevent autoinoculation, and increase patient quality of life. Treatment options for molluscum contagiosum include physician-administered and patient-administered therapies. Novel patient-administered treatment options allow administration in the privacy of a patient's home, providing added convenience and reducing patient embarrassment or stress. With the novel treatment opportunities currently available or in development, physicians are able to improve patient quality of life while providing patients with a convenient, well-tolerated, easily administered treatment regimen. This review summarizes the clinical diagnosis of molluscum contagiosum and provides a critical assessment of several current and emerging treatment options.


Genome-wide scan of African-American and white families for linkage to myopia.
To identify myopia susceptibility genes influencing common myopia in 94 African-American and 36 White families. A prospective study of families with myopia consisting of a minimum of two individuals affected with myopia. Extended families consisting of at least two siblings affected with myopia were ascertained. A genome-wide linkage scan using 387 markers was conducted by the Center for Inherited Disease Research. Linkage analyses were conducted with parametric and nonparametric methods. Model-free linkage analysis was performed maximizing over penetrance and over dominance (that is, fitting a wide range of both dominant and recessive models). Under the model-free analysis, the maximum two point heterogeneity logarithm of the odds score (MALOD) was 2.87 at D6S1009 in the White cohort and the maximum multipoint MALOD was 2.42 at D12S373-D12S1042 in the same cohort. The nonparametric linkage (NPL) maximum multipoint at D6S1035 had a P value of .005. An overall multipoint NPL score was obtained by combining NPL scores from both populations. The highest combined NPL score was observed at D20S478 with a significant P value of .008. Suggestive evidence of linkage in the White cohort mapped to a previously mapped locus on chromosome 11 at D11S1981 (NPL = 2.14; P = .02). Suggestive evidence of linkage to myopia in both African Americans and Whites was seen on chromosome 20 and became more significant when the scores were combined for both groups. The locus on chromosome 11 independently confirms a report by Hammond and associates mapping a myopia quantitative trait locus to this region.


Influence of polyvinylpyrrolidone quantity on the solubility, crystallinity and oral bioavailability of fenofibrate in solvent-evaporated microspheres.
The objective of this study is to explore the influence of polyvinylpyrrolidone (PVP) quantity on the solubility, crystallinity and oral bioavailability of poorly water-soluble fenofibrate in solvent-evaporated microspheres. Numerous microspheres were prepared with fenofibrate, sodium lauryl sulphate (SLS) and PVP using the spray-drying technique. Their aqueous solubility, dissolution, physicochemical properties and pharmacokinetics in rats were assessed. The drug in the solvent-evaporated microspheres composed of fenofibrate, PVP and SLS at the weight ratio of 1:0.5:0.25 was not entirely changed to the amorphous form and partially in the microcrystalline state. However, the microspheres at the weight ratio of 1:4:0.25 provided the entire conversion to the amorphous form. The latter microspheres, with an improvement of about 115 000-fold in aqueous solubility and 5.6-fold improvement in oral bioavailability compared with the drug powder, gave higher aqueous solubility and oral bioavailability compared with the former. Thus, PVP quantity played an important role in these properties of fenofibrate in the solvent-evaporated microspheres.


[The influence of left systolic ventricular function on right ventricular function after an acute myocardial infarct].
The aim of this study was to assess the interaction between left ventricular and right ventricular systolic function after acute myocardial infarction (AMI). The study population comprises 27 normal subjects and 71 patients assessed at predischarge (12 +/- 7 days) after AMI and divided into two subgroups, 24 with inferior AMI and 47 with non inferior AMI. The three groups were comparable for sex, age, heart rate and blood pressure. Right ventricular function was evaluated by two-dimensional assessment of tricuspid annular plane systolic excursion (TAPSE) and by Doppler analysis of right ventricular outflow tract. Left ventricular systolic function was evaluated by two-dimensional determination of ejection fraction and wall motion score index, and by Doppler analysis of left ventricular outflow tract. The overall AMI population showed reduced TAPSE, velocity-time integral (both p < 0.05) and peak velocity (p < 0.005) of right ventricular outflow tract, prolongation of Q-S2 interval and increase of pre-ejection period/acceleration time ratio (both p < 0.05) in comparison with normals. These alterations were accompanied by a decrease of left ventricular ejection fraction and increase of wall motion score index. (p < 0.0001) The changes of right ventricular indexes were confirmed in patients with inferior AMI who had also lower left ventricular ejection fraction (46 +/- 9%). Functional parameters of the right ventricle were not significantly modified in patients with non inferior AMI who had greater left ventricular ejection fraction (53 +/- 8.6%). In the overall AMI population, and in particular in inferior AMI, we found univariate relations between time-velocity integrals of left ventricular and right ventricular outflow tract and between left ventricular ejection fraction and TAPSE. Only in inferior AMI creatinkinase peak was related to time-velocity integral of right ventricular outflow tract (r = -0.59, p < 0.01). In conclusion, the magnitude of right ventricular systolic impairment developing after left ventricular AMI depends on the degree of left ventricular dysfunction, likewise by changes of hemodynamic load imposed to the right ventricle. AMI location and, only in inferior AMI, infarct extension participate in determining this dysfunction.


Naturally together: pitch-height and brightness as coupled factors for eliciting the SMARC effect in non-musicians.
Pitch-height is often labeled spatially (i.e., low or high) as a function of the fundamental frequency of the tone. This correspondence is highlighted by the so-called Spatial-Musical Association of Response Codes (SMARC) effect. However, the literature suggests that the brightness of the tone's timbre might contribute to this spatial association. We investigated the SMARC effect in a group of non-musicians by disentangling the role of pitch-height and the role of tone-brightness. In three experimental conditions, participants were asked to judge whether the tone they were listening to was (or was not) modulated in amplitude (i.e., vibrato). Participants were required to make their response in both the horizontal and the vertical axes. In a first condition, tones varied coherently in pitch (i.e., manipulation of the tone's F0) and brightness (i.e., manipulation of the tone's spectral centroid); in a second condition, pitch-height varied whereas brightness was fixed; in a third condition, pitch-height was fixed whereas brightness varied. We found the SMARC effect only in the first condition and only in the vertical axis. In contrast, we did not observe the effect in any of the remaining conditions. The present results suggest that, in non-musicians, the SMARC effect is not due to the manipulation of the pitch-height alone, but arises because of a coherent change of pitch-height and brightness; this effect emerges along the vertical axis only.


An innovative microelectrode fabricated using photolithography for measuring dissolved oxygen distributions in aerobic granules.
In this work an innovative microelectrode was successfully fabricated using photolithography for determination of dissolved oxygen distributions in aerobic granules, which were sampled from a nitrifying sequencing batch reactor. A negative photoresist, SU-8, was used as a substrate for the microelectrode and a 70 microm wide needle was photopatterned on it. The microelectrode could be renewed several times. Cyclic voltammetry analysis and dissolved oxygen measurement demonstrated that the microelectrode was stable and reliable. Dissolved oxygen distribution in a nitrifying granule was successfully monitored with the microelectrode. The profiles indicated that the main active part of the nitrifying granule was the upper 150 microm layer. Using the procedures developed in this work, microelectrodes of the desired shape could be constructed with precise size control at micrometers-scale.


The use of iron in patients on chronic dialysis: mistake and misconceptions.
Anemia is the most common hematologic abnormality in patients with chronic renal failure. The reasons for anemia in chronic renal failure are many and include erythropoietin and iron deficiencies, inflammation, infection, aluminum toxicity, and hyperparathyroidism. Iron deficiency alone affects more than 50% of patients on dialysis, and the estimated iron loss for these patients is 1.5 to 3 grams per year. The use of erythropoietin has also uncovered iron deficiency in a multitude of patients. Iron and erythropoietin supplementation has often restored normal or near-normal levels of hematocrit in these patients and has therefore improved some of the symptoms classically connected with chronic renal failure, such as fatigue, cold intolerance, and mental sluggishness, among others. Resistance to erythropoietin is frequently observed in the maintenance care for dialysis patients, and the most common reason is iron deficiency. It is important to understand the physiology of renal anemia, erythropoiesis and iron metabolism in order to avoid mistakes and misconceptions in the management of iron in chronic dialysis patients. In this article, we review several mistakes, misconceptions, practices, and guidelines in iron supplementation therapy. We also review the physiology of anemia in renal disease and the importance of erythropoietin and iron in causing anemia and discuss recent Dialysis Outcomes Quality Initiative (DOQI) guidelines on the topic.


Molecular mechanism of chemical modification of cellular nucleic acid bases by 4-hydroxyaminoquinoline 1-oxide.
The O-acyl derivative of 4-hydroxyaminoquinolone, the proposed ultimate metabolite in carcinogenesis by the parent compound, was proposed to undergo a nitrogen-oxygen heterolysis to produce three types of reaction intermediates: a nitrenium, a carbonium, and nitrene intermediates, which were considered to give N(4)-substituted 4-aminoquinoline 1-oxide (4-AQO), 3-substituted 4-AQO, and 4-AQO, respectively, in reactions with nucleophiles including nucleic acid bases. Chemical modification of cellular DNA by this carcinogen is discussed.


Oxygenation of patients undergoing ophthalmic surgery under local anaesthesia.
The oxygenation of 30 patients undergoing elective ophthalmic surgery without sedation whilst breathing air was studied and was compared with two methods of oxygen supplementation. Arterial oxygen saturation, inspired and expired oxygen and carbon dioxide were analysed. The delivery of oxygen at 21.min-1 via nasal cannulae was shown to be superior to a method which directed oxygen from under the surgical drapes.


Efficacy and safety of low power holmium laser enucleation of the prostate: A prospective short- and medium-term single-blind randomized trial.
We evaluated the efficacy and safety of mid-term follow-up in low-power (LP) Holmium laser enucleation of the prostate (HoLEP) compared with high-power (HP) surgery for benign prostatic hyperplasia (BPH). This prospective, single-blind, randomized controlled study was conducted between September 2020 and April 2021. Ninety male patients >50 years who underwent HoLEP for BPH were randomly assigned to HP (80 W/2 J/40 Hz) and LP (24 W/2 J/12 Hz) groups. The primary endpoint was the total International Prostate Symptom Score (IPSS) six months after surgery. The secondary endpoints were perioperative results and postoperative outcomes at two weeks, three and six months after the surgery, including Clavien-Dindo complication classification. At six months after HoLEP, 41 and 42 patients were followed up in the HP and LP groups, respectively. There was no difference in the preoperative characteristics between the two groups. The prostate volumes were 67.1±23.7 mL for the HP group and 64.3±25.7 mL for the LP group (p=0.592), respectively. Although the total operative time was significantly longer by 13.1 minutes in the LP group (47.8±20.3 min vs. 60.9±23.3 min, p=0.006), the total delivered energy was significantly lower, which was only about 68% of the HP group (58.2±23.9 kJ vs. 39.9±13.2 kJ, p<0.001). Surgical outcomes significantly improved postoperatively in both groups compared to baseline, except for storage symptoms. Improvement in IPSS storage subscore was observed from the immediate postoperative 2 weeks in the LP group (8.1±3.1 to 6.9±3.8, p<0.001), whereas there was no significant recovery in the HP group (8.0±3.2 to 7.7±3.4, p=0.842). In the 6-month follow, there was no significant difference between the two groups in the IPSS total score (5.9±5.6 vs. 7.3±5.3, p=0.260) as well as IPSS storage subscore. In addition, there was no significant difference in postoperative complications, including bleeding or urinary incontinence, between the two groups. The HoLEP procedure performed using an LP laser device resulted in lower total delivered energy, faster recovery, and significantly improved surgical outcomes up to mid-term follow-up. There was no difference in efficiency or safety between the HP device system.


Postmenopausal pregnancy? Evaluation of elevated hCG in a 59-year-old woman.
Slightly elevated serum human chorionic gonadotropin (hCG) can be a normal finding in postmenopausal women. We report a case of a 59-year-old woman with a history of abnormal uterine bleeding who presented with a concern for pregnancy after developing nausea and vomiting a few weeks after unprotected intercourse. Although pregnancy was extremely unlikely, hCG was obtained in order to reassure the patient since she reported that her mother conceived at the age of 60. Serum hCG was positive, prompting concern for malignancy versus pregnancy. Stable serum hCG levels, elevated follicle-stimulating hormone and negative transvaginal ultrasound ruled out both malignancy and pregnancy. Positive serum pregnancy test and hCG elevation was attributed to normal postmenopausal state.


HBsAg-negative chronic active hepatitis and mixed connective tissue disease syndrome. An unusual association observed in two patients.
Two patients are described who suffered from both HBsAg-negative chronic active hepatitis and mixed connective tissue disease syndrome. The diagnosis of liver disease was made prior to the diagnosis of collagenosis in one of the patients, whereas the opposite was the case in the other. In spite of the fact that symptoms and laboratory data suggesting both diagnoses were present from the moment of presentation, there was a considerable delay in establishing the second diagnosis in both patients. To our knowledge, this is the first report on an association between chronic active hepatitis and mixed connective tissue disease syndrome. It illustrates the difficulties when diagnosing overlap conditions.


Amination of black liquor and the application in the ready-mixed wet mortar.
In order to extend the application of black liquor (BL), amino group was introduced in lignin through Mannich reaction. The structure of the aminated black liquor (ABL) was characterized with FT-IR, elemental analysis, the zeta potential and the inherent viscosity. The foam generated by ABL was more stable, for the surface tension was lower. The results of the mortar test indicated that the water-retention rate of the fresh mortar incorporated with 0.3 wt% ABL was 89.1%; the consistency loss was about 39.7% after 4 h. When the dosage was less than 0.3 wt%, ABL could increase the bond strength of the hardened mortars. The results showed that ABL could be used as an effective ready-mixed wet mortar admixture. This study not only provided a new method to develop new mortar admixture, but also alleviated the pollution of BL.


Primary lymph node gastrinoma: A single institution experience.
Gastrinomas are rare neuroendocrine tumors that ectopically secrete gastrin and classically originate within the duodenum or pancreas. The presence of primary lymph node gastrinoma is controversial. We report on a single institution's experience with gastrinoma, with focus on primary lymph node tumors. Patients who underwent operative resection of gastrinoma between 1992 and 2016 at a single institution were identified. A diagnosis of primary lymph node gastrinoma was defined as tumor confined to one or more resected peripancreatic lymph nodes, negative localization for any extra-nodal disease and normal gastrin postresection. In the study, 39 consecutive patients underwent operative resection of gastrinoma. Mean age was 53 years and 49% were male. 93% of patients had successful preoperative localization. Furthermore, 19 patients (49%) underwent enucleation of their tumor and 14 (35.9%) a pancreatic resection. Overall 5- and 10-year survival for all patients was 80.8% and 60.7%, respectively. Primary lymph node gastrinoma was identified in 11 cases (28.2%). The presentation of primary lymph node and non-primary lymph node patients were similar. There was no significant difference in operation type, tumor size, or overall survival. At median follow-up of 59 months, patients with primary lymph node gastrinoma were less likely to have persistent or recurrent disease (9.1% vs 42.9%, P = .04). This series supports the existence of primary lymph node gastrinomas, and indicates that as many as 1 in 4 patients with gastrinoma have this form of the disease. This entity should be considered when an isolated pathologic lymph node is identified, although thorough exploration is still recommended to exclude other occult disease.


Generalizability of the Proportional Recovery Model for the Upper Extremity After an Ischemic Stroke.
Spontaneous neurological recovery after stroke is a poorly understood process. The aim of the present article was to test the proportional recovery model for the upper extremity poststroke and to identify clinical characteristics of patients who do not fit this model. A change in the Fugl-Meyer Assessment Upper Extremity score (FMA-UE) measured within 72 hours and at 6 months poststroke served to define motor recovery. Recovery on FMA-UE was predicted using the proportional recovery model: ΔFMA-UEpredicted = 0.7·(66 - FMA-UEinitial) + 0.4. Hierarchical cluster analysis on 211 patients was used to separate nonfitters (outliers) from fitters, and differences between these groups were studied using clinical determinants measured within 72 hours poststroke. Subsequent logistic regression analysis served to predict patients who may not fit the model. The majority of patients (~70%; n = 146) showed a fixed proportional upper extremity motor recovery of about 78%; 65 patients had substantially less improvement than predicted. These nonfitters had more severe neurological impairments within 72 hours poststroke (P values <.01). Logistic regression analysis revealed that absence of finger extension, presence of facial palsy, more severe lower extremity paresis, and more severe type of stroke as defined by the Bamford classification were significant predictors of not fitting the proportional recovery model. These results confirm in an independent sample that stroke patients with mild to moderate initial impairments show an almost fixed proportional upper extremity motor recovery. Patients who will most likely not achieve the predicted amount of recovery were identified using clinical determinants measured within 72 hours poststroke.


An epoxide hydrolase involved in the biosynthesis of an insect sex attractant and its use to localize the production site.
Epoxide hydrolases (EHs) are enzymes occurring in virtually any living organism. They catalyze the hydrolysis of epoxide containing lipids and are involved in crucial mechanisms, such as the detoxification of xenobiotics or the regulation of inflammation and blood pressure. Here, we describe a function of a putative EH gene in the biosynthesis of a sex attractant in the jewel wasp Nasonia vitripennis and use this gene to localize the site of pheromone production. Males of this parasitic wasp release a mixture of (4R,5R)-( threo-) and (4R,5S)-( erythro-)5-hydroxy-4-decanolide (HDL) to attract virgin females. Using a stable isotope labeled precursor, we demonstrated that vernolic acid ( erythro-12,13-epoxy-octadec-9Z-enoic acid) is converted by N. vitripennis males to threo-HDL. This suggested the involvement of an EH in hydrolyzing the fatty acid epoxide under inversion of the stereochemistry into the respective diol, which might be further processed by chain shortening and lactonization to HDL. We cloned a putative N. vitripennis EH gene (Nasvi-EH1) encoding 470 amino acids and localized its transcripts in the male rectal papillae by in situ RT-PCR. Chemical analyses and histological studies confirmed that males synthesize the sex attractant in the rectal vesicle and release it via the anal orifice. Involvement of Nasvi-EH1 in HDL biosynthesis was established by RNAi-mediated gene silencing. Injection of Nasvi-EH1 dsRNA into male abdomens inhibited pheromone biosynthesis by 55% and suppressed the targeted gene transcripts in the rectal vesicle by 95%.


Desmethionine alkylamide bombesin analogues: a new class of bombesin receptor antagonists with potent antisecretory activity in pancreatic acini and antimitotic activity in Swiss 3T3 cells.
Bombesin-related peptides have a large number of physiological functions as well as having an autocrine growth mechanism for the regulation of small cell lung cancer cells. In the present study we have synthesized 21 des-Met amide or alkylamide analogues of bombesin and compared their abilities to function as bombesin receptor antagonists in guinea pig pancreatic acini and Swiss 3T3 cells with those of the previously most potent antagonist described, [Leu13 psi(CH2NH)Leu14]bombesin (analogue I). All des-Met analogues functioned as antagonists. Bn(1-13)NH2 was approximately equipotent to I (Ki = 60-80 nM) whereas Bn(6-13)NH2 was 30-fold less potent (Ki = 1800 nM). Formation of an ethylamide, Bn(6-13)ethylamide, increased the potency 30-fold such that this octapeptide was equipotent to I. The addition of a D-Phe6 moiety to I did not change potency but caused a 30-fold increase in potency of Bn(6-13)NH2 and a 8-fold increase in the potency of Bn(6-13)ethylamide (Ki = 16 nM). Additional studies of both NH2- and COOH-terminal alterations in Bn(6-13)NH2 demonstrated that the most potent antagonist was [D-Phe6]Bn(6-13)propylamide (PA), having IC50's of 1.6 nM and 0.8 nM for bombesin-stimulated amylase release and Swiss 3T3 cell growth, respectively. Detailed studies of the most potent amide analogue, [D-Phe6]Bn(6-13)NH2, and alkylamide analogue, [D-Phe6]Bn(6-13)PA, demonstrated that these analogues functioned as competitive antagonists and that their action was selective for the bombesin receptor. These results demonstrate that, as with CCK- and gastrin-related peptides, the C-terminal amino acid is important for initiating a biologic response but not essential for determining receptor affinity.(ABSTRACT TRUNCATED AT 250 WORDS)


Individual and environmental factors that influence longevity of newcomers to nursing and midwifery: a scoping review.
The objective of this review was to identify the literature and map the individual and environmental factors that influence registered nurses' and midwives' decision to stay or leave their professions within the first 3 years of practice. Nursing and midwifery workforce sustainability is an international concern. One aspect is the retention of new registered nurses and midwives in their first years of practice. Several factors are thought to influence the decisions of new registered nurses and midwives to leave or stay in their professions. This review sought to identify and map those factors to enable further research for workforce sustainability development strategies. The study cohort included registered nurses and midwives in their first 3 years of practice, which we called newcomers . Nurses who were required to work under the supervision of registered nurses and midwives (eg, enrolled nurses, licensed practical nurses, and licensed vocational nurses) were excluded. Papers were only included if they explored individual or environmental factors influencing nurses' decision to stay in or leave the professions of nursing or midwifery. Studies could be from any country or care environment, and participants were newcomers providing direct clinical care. Newcomers employed in other health roles, such as education, research, administration, and non-nursing/midwifery roles were excluded. All research designs and peer-reviewed papers were included; policy documents were excluded. The date of inclusion was from the earliest publication on this topic, which was 1974 to the date of the search. The JBI methodology for scoping reviews was followed, and reporting followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidance. The search strategy aimed to locate published and unpublished primary studies, reviews, and text and opinion papers. The initial search of relevant databases was conducted in January 2020 and updated in January 2022. Reference lists of included articles were also screened. Following data extraction, descriptive qualitative content analysis was undertaken. Twelve articles from 11 studies were included in this review. They were published between 2005 and 2020 and originated from 5 countries. Two studies were observational, 3 were cross-sectional, 5 were longitudinal studies, 1 was a pre- and post-program evaluation, and 1 was a scoping review. All studies focused on registered nurses: no publications on registered midwives met the inclusion criteria. Individual factors we identified that impact newcomers' intention to stay in or leave the profession included physical and psychological health, professional identity, professional commitment, and development. Environmental factors included workplace culture, engagement, and management. Professional self-image, identity, and a sense of pride in the profession are important components of newcomer retention. Strategies that positively support transition and create realistic expectations were highlighted. Managers play an important role in registered nurse retention as they can influence many of the newcomers' experiences. It is concerning that no studies about newcomer midwives were found. Many studies explored turnover or intention to leave the job/employer rather than the profession. These are important considerations for future research.


Applicability of health promoting lifestyle profile-II for postmenopausal women in Sri Lanka; a validation study.
Health Promoting Lifestyle Profile-II (HPLP-II), developed in the West, evaluates 52 health promoting behaviors (HPB) under six subscales. In this study we evaluated the applicability of HPLP-II to assess the HPB of postmenopausal women (PMW) conversant in the Sinhala language in Sri Lanka. The Sinhala version of HPLP-II was adapted following standard methodology of cross cultural adaptation. It included forward and backward translations, review by an expert group, focus group discussion and pre-testing. It was self-administered among randomly selected healthy, Sinhalese, community-dwelling PMW (n = 245, aged 55.9 ± 3.4 years), along with the Short Form 36 (SF-36) survey. The Sinhala version of HPLP-II was re-administered among a subsample (n = 105) after two weeks of first administration. Psychometric properties - reliability and validity, were evaluated. In the Sinhala version of HPLP-II, both internal consistency (Cronbach's alpha = 0.98) and test-retest reliability (intra class correlation / ICC = 0.98, 95%CI = 0.97-0.99) were high. Structural validity assessment with Factor analysis using Principal Component Analysis extracted seven factors explaining 80.65% cumulative variance with few exceptions from the original version. Health responsibility (HR) and spiritual growth (SG) subscales of HPLP-II and physical and psychological health dimensions scores of SF-36 scores correlated significantly (r > 0.63, p < 0.001) ensuring strong concurrent validity. The Sinhala version of HPLP-II adapted by us is a tool with high reliability and validity.


[Proximal femur fractures in the elderly in The Netherlands during the period 1991-2004: incidence, mortality, length of hospital stay and an estimate of the care capacity needed in the future].
To assess the incidence of operations for neck and pertrochanteric femur fractures during the last 15 years and to estimate the future demand for such operations in The Netherlands. Retrospective. For the years 1991, 1995, 2000 and 2004, the following anonymised data were collected in the National Medical Registry of Prismant for all patients admitted to Dutch hospitals for a hip fracture: age-group, gender, length of pre- and postoperative hospital stay, destination after discharge and hospital mortality. These data were related to demographic data for the Dutch population from Statistics Netherlands (CBCS) and to estimates for the Dutch population in the future from Primos Prognostic Data. The average absolute increase in the period 1991-2004 was linear, with 230 fractures per year. Women were operated for a hip fracture 1.5-2 times as often as men in the same age range. The age-specific incidence remained constant over the years but the absolute number of elderly persons per age group increased. The average length of pre- and postoperative hospital stay was reduced by half during the period under investigation. The postoperative hospital mortality decreased from 8.1% in 1991 to 5.6% in 2004, and was 1.5 times as high for men aged 70 years or over as for women of the same age group. In 2004 as compared to 1991, 2.5 times as many patients were discharged to a nursing home. In view of the increasing age of the population, the total number of operated hip fractures can be expected to be 20,200 in the year 2010 and 23,900 in the year 2020. In the period 1991-2004 there was an annual increase of 230 operations for proximal femur fractures that was closely related to the ageing of the Dutch population. During the years under investigation, the incidence in the same age range was higher in women, but men had a higher hospital mortality. It is estimated that the decreasing hospital mortality and the decrease in the length of hospital stay will increase the need for nursing-home care for this category of patients.


Molecular mechanisms linking stress and insulin resistance.
To date, there is ample evidence to support the strong relationship between stress and insulin resistance. While diabetes mellitus acts as a potent stress inducer, stress may be an upstream event for insulin resistance as well. It is widely recognized that diabetes mellitus is more prevalent among people who have a stressful lifestyle; however, the underlying mechanisms are not well understood. In the current study, we surveyed the scientific literature for possible interactions between stress and insulin resistance and found that stress can impair glucose homeostasis, working through at least six molecular pathways.


Vascular image in autoimmune pancreatitis by contrast-enhanced color-Doppler endoscopic ultrasonography: Comparison with pancreatic cancer.
In autoimmune pancreatitis (AIP), veins of various sizes are highly affected by obliterative phlebitis without damage to arteries, in contrast, the involvement of both arteries and veins is observed in the mass of pancreatic cancer. A vascular image without blooming artifact in the pancreas is clearly observed in the directional eFLOW (Prosound α10, Aloca Co., Tokyo, Japan) color mode using contrast-enhanced color-Doppler endoscopic ultrasonography (CC-EUS) despite perfusion of the contrast media. The aim of this study was to compare the vascular structure of AIP with that of pancreatic cancer using CC-EUS. We evaluated the perfusion image and the vascular image of the mass in AIP patients (11) with an increase in serum IgG4 levels (477.3 ± 314.2 IU/mL) and in pancreatic cancer patients (11) with elevated serum CA19-9 levels (49839.0 ± 80061.6 mg/dl), on CC-EUS. Perfusion images were obtained at 20-30 s after injection of a contrast agent, Sonazoid (GE Healthcare AG, Oslo, Norway), by extended pure harmonic detection mode and were assessed as to homogeneity or heterogeneity (containing partial low echoic areas or multiple spotty low echoic areas) enhancement. The vascular image was assessed in the directional eFLOW color mode despite perfusion of the contrast media (40-50 s after injection of Sonazoid) as to the presence of a dendritic vessel network or only a few feeder vessels. The parameters for imaging were as follows: Mechanical index, 0.22-0.24; transmission frequency, 5.0 MHz; and receiving frequency, 5.0 MHz. The Chi-square test or Fisher's exact test was used for comparison of categorical data of the two groups when appropriate. This study was approved by the institutional review board of Sendai City Medical Center. All subjects gave informed consent. A homogenous pattern in perfusion imaging was seen in 73% of patients with AIP (8/11) and 55% of those with pancreatic cancer (6/11). The rates were not significantly different between the two groups (P = 0.33). In the other patients with a heterogenous pattern, multiple spotty low echoic areas were seen in 33% (1/3) and 80% (4/5) in each group, respectively. A dendritic vascular pattern in the eFLOW color mode was seen in 82% (9/11) of patients with AIP, but was not seen in any of patients with pancreatic cancer. The other patients with AIP (18%) and all patients with pancreatic cancer showed only a few feeder vessels in the mass on CC-EUS. The eFLOW color mode using Sonazoid may be useful for evaluating the vascular structure of AIP for differential diagnosis from pancreatic cancer.


Prevalence and correlates of untreated human immunodeficiency virus type 1 infection among persons who have died in the era of modern antiretroviral therapy.
We evaluated all human immunodeficiency virus (HIV)-related deaths over the period 1 January 1995-31 December 2001 in a Canadian province in which all HIV care and antiretroviral therapy are provided free of charge. Persons who had received antiretroviral drugs before death were compared with those who had died without ever receiving HIV treatment, by fitting a logistic model. Overall, 1239 deaths were attributed to HIV infection during the study period. Of these, 406 (32.8%) occurred among persons who had never received any HIV treatment. In adjusted analyses, aboriginal ethnicity, female sex, and lower median income were negatively associated with receiving HIV treatment before death. Furthermore, among the 833 individuals who received treatment before death, only 379 (45.5%) received antiretroviral medication >or=75% of the time during their first year receiving therapy. The data demonstrate the need for novel interventions to expand HIV care to specific populations.


Surgical suite to pediatric intensive care unit handover protocol: implementation process and long-term sustainability.
The article reports the long-term sustainability of a standardized transfer protocol from cardiac surgical suite to the pediatric intensive care unit. Using rapid process improvement technique, the original mean defect rate per handover decreased from 13.2 to 0 and 0.3, 12, and 24 months postimplementation, respectively. This study stresses the importance of long-term assessment to control for possible observation biases; it also illustrates a successful implementation strategy that used video recording to engage staff in identifying solutions to the observed defects.


Clinical features and results of management of superior vena cava syndrome secondary to lymphoma.
Thirty-six of 915 patients with non-Hodgkin's lymphoma presented with superior vena cava syndrome (SVCS). The histologic types associated with SVCS were diffuse large cell in 23 patients, lymphoblastic in 12, and follicular large cell in one patient. Radiotherapy alone appeared equal to chemotherapy alone or in combination with radiotherapy in achieving relief of SVCS symptoms. Chemotherapy alone or in combination with radiotherapy was superior to radiotherapy alone in prolonging relapse-free survival and overall survival. No differences in relapse-free survival and survival were found between the patients treated with chemotherapy alone and those treated with chemotherapy and radiotherapy, but the addition of radiotherapy appeared to prevent local relapses in the group with large-cell lymphoma. The presence of symptoms of involvement of other mediastinal structures such as dysphagia, hoarseness, or stridor (DHS), a higher grade of intensity, and a shorter duration of symptoms (less than or equal to 2 weeks) appeared to adversely influence relapse-free survival and survival. The following conclusions were made: (1) a histologic diagnosis before the onset of treatment is desirable and feasible in patients presenting with SVCS except in those with severe respiratory distress, (2) both chemotherapy and radiotherapy are equally effective in alleviating the symptoms of SVCS, and (3) combined modality treatment with chemotherapy and radiotherapy results in a lower frequency of local relapses compared to chemotherapy alone but survival was similar in both groups.


Sedentary behaviour is associated with increased long-term cardiovascular risk in patients with rheumatoid arthritis independently of moderate-to-vigorous physical activity.
Rheumatoid Arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD). The physical dysfunction symptomatic of RA means people living with this disease spend large periods of the day sedentary, which may further elevate their risk of CVD. The primary aim of this study was to investigate relationships between objectively assessed sedentary behaviour patterns and light physical activity (LPA) with 10-year risk of CVD. Secondary aims were to explore the role of sedentary behaviour patterns and LPA for individual CVD risk factors and functional disability in RA. The extent to which associations were independent of moderate-to-vigorous physical activity (MVPA) engagement was also examined. Baseline data from a subsample of participants recruited to the Physical Activity in Rheumatoid Arthritis (PARA) study were used to answer current research questions. Sixty-one patients with RA (mean age (± SD) = 54.92 ± 12.39 years) provided a fasted blood sample and underwent physical assessments to evaluate factors associated with their cardiovascular health. Sedentary behaviour patterns (sedentary time, sedentary bouts, sedentary breaks), LPA and MVPA were measured via 7-days of accelerometry. Ten-year CVD risk was computed (Q-risk-score2), and functional disability determined via questionnaire. Regressions revealed significant positive associations between sedentary time and the number of sedentary bouts per day ≥20 min with 10-year CVD risk, with the reverse true for LPA participation. Associations were independent of MVPA engagement. Promoting LPA participation and restricting sedentary bouts to <20 min may attenuate long-term CVD risk in RA, independent of MVPA engagement. ISRCTN04121489 (retrospectively registered 19/10/2012).


Patient-Reported Outcomes Measurement Information System Validation in Hip Arthroscopy: A Shift Towards Reducing Survey Burden.
Background The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to provide measures of patient-reported symptoms and healthcare outcomes across a variety of conditions in an easily accessible manner. The purpose of this study was to validate PROMIS against traditional legacy measures in patients undergoing hip arthroscopy for femoral acetabular impingement (FAI). Methodology Outcome measures collected pre- and post-operatively included PROMIS Pain Interference (PI) and Physical Function (PF), modified Harris Hip Score (mHHS), Hip Outcome Score-Activities of Daily Living and Sport (HOS-ADL and HOS-Sport), Nonarthritic Hip Score (NAHS), and Visual Analog Scale (VAS). Pearson's correlation coefficients were calculated between each outcome measure. Results Strong correlations were observed between the PROMIS PF T-Score and the mHHS (r = 0.64-0.83, p < 0.0001), HOS-ADL (r = 0.54-0.81, p < 0.0001), HOS-Sport (r = 0.55-0.74, p < 0.0001), and NAHS (r = 0.61-0.78, p < 0.0001) measurement tools. PROMIS Computer Adaptive Testing PI T-Score and VAS also demonstrated a strong correlation (r = 0.64-0.80, p < 0.0001). Conclusions PROMIS PF scores correlate strongly with mHHS, HOS-ADL, HOS-Sport, and NAHS scores at all time points. Likewise, PROMIS PI scores correlate strongly with VAS pain scores. On average, patients completing PROMIS need to fill out only four or five questions. This study supports the use of PROMIS as an efficient, valid outcome tool for patients with FAI undergoing hip arthroscopy.


Detection of target DNA with a novel Cas9/sgRNAs-associated reverse PCR (CARP) technique.
This study develops a new method for detecting target DNA based on Cas9 nuclease, which was named as CARP, representing CRISPR- or Cas9/sgRNAs-associated reverse PCR. This technique detects target DNA in three steps: (1) cleaving the detected DNA sample with Cas9 in complex with a pair of sgRNAs specific to target DNA; (2) ligating the cleaved DNA with DNA ligase; (3) amplifying target DNA with PCR. In the ligation step, the Cas9-cut target DNA was ligated into intramolecular circular or intermolecular concatenated linear DNA. In the PCR step, the ligated DNA was amplified with a pair of reverse primers. The technique was verified by detecting HPV16 and HPV18 L1 genes in nine different human papillomavirus (HPV) subtypes. The technique also detected the L1 and E6-E7 genes of two high-risk HPVs, HPV16 and HPV18, in the genomic DNA of two HPV-positive cervical carcinoma cells (HeLa and SiHa), in which no L1 and E6-E7 genes were detected in the HPV-negative cervical carcinoma cell, C-33a. By performing these proof-of-concept experiments, this study provides a new CRISPR-based DNA detection and typing method. Especially, the CARP method developed by this study is ready for the clinical HPV detection, which was supported by the final clinical sample detection. Graphical abstract CRISPR-associated reverse PCR (CARP) can be used to detect and type target DNA in a simple three-step procedure, cutting, ligation, and amplification.


Ovarian tissue cryopreservation for patients with premature ovary insufficiency caused by cancer treatment: optimal protocol.
Objective: Premature ovary insufficiency is frequent after chemotherapy/radiotherapy in cancer patients. Ovarian tissue (OT) cryopreservation and later retransplantation, the routine method in Europe, has recently been implemented at the first center in China. We investigated the protective effect of the antioxidant N-acetyl-l-cysteine (NAC) during the decisive freezing-thawing steps. Methods: Fifteen OT samples were obtained from each of 13 cancer patients prospectively and randomly assigned to a control group and four groups with different NAC concentrations (Group 1, 0 mM NAC; Group 2, 0.5 mM NAC; Group 3, 1 mM NAC; Group 4, 5 mM NAC; Group 5, 25 mM NAC). After thawing, the follicle viability, DNA fragmentation, levels of reactive oxygen species (ROS), and total antioxidant capacity (TAC) were evaluated. Results: OT cryopreserved and thawed with 25 mM NAC (Group 5) has the lowest proportion of apoptotic stroma cells, but the worst follicle viability. The other four groups show similar anti-apoptosis and good follicle viability. Group 4 presented the lowest ROS and highest TAC levels. Conclusions: OT cryopreserved and thawed in medium supplemented with 5 mM NAC shows the highest antioxidant and lowest ROS capability, good apoptotic parameters, and follicle viability. Our results need to be confirmed in larger patient cohorts prior to being accepted as a standard protocol.


Shoot-Root Interplay Mediates Defoliation-Induced Plant Legacy Effect.
Shoot defoliation by grazers or mowing can affect root traits of grassland species, which may subsequently affect its aboveground traits and ecosystem functioning (e.g., aboveground primary production). However, experimental evidence for such reciprocal feedback between shoots and roots is limited. We grew the perennial grass Leymus chinensis-common across the eastern Eurasian steppe-as model species in a controlled-hydroponics experiment, and then removed half of its shoots, half of its roots, or a combination of both. We measured a range of plant aboveground and belowground traits (e.g., phenotypic characteristics, photosynthetic traits, root architecture) in response to the shoot and/or root removal treatments. We found the regenerated biomass was less than the lost biomass under both shoot defoliation and root severance, generating a under-compensatory growth. Root biomass was reduced by 60.11% in the defoliation treatment, while root severance indirectly reduced shoot biomass by 40.49%, indicating a feedback loop between shoot and root growth. This defoliation-induced shoot-root feedback was mediated by the disproportionate response and allometry of plant traits. Further, the effect of shoot defoliation and root severance on trait plasticity of L. chinensis was sub-additive. That is, the combined effects of the two treatments were less than the sum of their independent effects, resulting in a buffering effect on the existing negative influences on plant persistence by increased photosynthesis. Our results highlight the key role of trait plasticity in driving shoot-root reciprocal feedbacks and growth persistence in grassland plants, especially perennial species. This knowledge adds to earlier findings of legacy effects and can be used to determine the resilience of grasslands.


Clinical efficacy of a centric relation occlusal splint and intra-articular liquid phase concentrated growth factor injection for the treatment of temporomandibular disorders.
The agony that accompanies the incidence and symptoms of temporomandibular disorders (TMDs) is an important concern in the oral and maxillofacial region. The objective of this study was to explore the clinical findings after centric relation occlusal splint (CROS) treatment and intra-articular injection treatment with liquid phase concentrated growth factors (LPCGFs) in patients with disc displacement without reduction (DDWOR).The group under investigation of this retrospective cohort study included patients with DDWOR who received treatment from April 2014 until March 2016. The predictor variable was the therapeutic method. The outcome variables included joint crepitus sound, visual analog scale (VAS) of temporomandibular joint (TMJ) arthralgia, TMD-associated headache, myofascial pain with referral, deviation of the mandible during opening (DoM), and maximal interincisal opening (MIO). At the stage of CROS treatment, evaluation of all variables adopted the individual as the unit; at the stage after LPCGF injection, the evaluation of joint sound adopted the joint as the unit, whereas the other variables adopted the individual as the unit.Among the 29 patients, 6 (20.68%) were males and 23 (79.31%) were females. Distribution by age ranged from 15 to 84 years (mean age 39.55 ± 15.49 years). After CROS treatment, except for the joint crepitus sound, which failed to achieve significant improvement (P > 0.05), other symptoms, such as DOM, TMD-associated headache, myofascial pain with referral, TMJ arthralgia, and MIO, all achieved statistically significant improvements (P < 0.05). After 2 mL of LPCGF was injected once after CROS treatment, 26 joint crepitus sound symptoms were relieved (P < 0.001) after an average of 48.5 ± 64.1 days.CROS alone can alleviate TMD clinical symptoms, except for the joint crepitus sound. Approximately 72.2% of joint crepitus sounds could be improved within 48 days, on average, once 2 mL of LPCGF was injected. Comparisons were still required in the future, with the effects of other therapeutic methods.


In vivo MR studies of glycine and glutathione metabolism in a rat mammary tumor.
The metabolism of glycine into glutathione was monitored noninvasively in vivo in intact rat mammary adenocarcinomas (R3230Ac) by MRI and MRS. Metabolism was tracked by following the isotope label from intravenously infused [2-(13)C]-glycine into the glycinyl residue of glutathione. Signals from [2-(13)C]-glycine and γ-glutamylcysteinyl-[2-(13)C]-glycine ((13)C-glutathione) were detected by nonlocalized (13)C spectroscopy, as these resonances are distinct from background signals. In addition, using spectroscopic imaging methods, heterogeneity in the in vivo tumor distribution of glutathione was observed. In vivo spectroscopy also detected isotope incorporation from [2-(13)C]-glycine into both the 2- and 3-carbons of serine. Analyses of tumor tissue extracts showed single- and multiple-label incorporation from [2-(13)C]-glycine into serine from metabolism through the serine hydroxymethyltransferase and glycine cleavage system pathways. Mass spectrometric analysis of extracts also showed that isotope-labeled serine is further metabolized via the trans-sulfuration pathway, as (13)C isotope labels appear in both the glycinyl and cysteinyl residues of glutathione. Our studies demonstrate the use of MRI and MRS for the monitoring of tumor metabolic processes central to oxidative stress defense.


[Duration of the retention of iodine contrast agents in the body--an x-ray fluorescence analytical determination].
X-ray fluorescence is able to detect iodine as it is used in contrast agents with low concentrations in vivo in man. Measurements of the time dependence of this concentration after angiographies show that one must distinguish between patients with a defect in the blood-brain barrier and those with an angiographically demonstrated arterial flow reduction.


Comparing executive functions between patients with chronic asthma and healthy subjects.
Allergic diseases have different levels of prevalence all over the world. Among them, asthma is the most common chronic disease. Up to now, little attention has been paid to the impact of this chronic disease on people's executive functions. The present study aimed at comparing the executive functions in patients with chronic asthma and healthy subjects. The study population was patients with chronic asthma who were referred to Al-Zahra hospital in Isfahan Province and their visitors who were assigned as the control group. Thirty patients with chronic asthma and 30 patient visitors were enrolled in this study, and three software programs (Wisconsin, Stroop, and Continuous Performance Tests) were used. The results of multivariate variance analysis showed that there is a significant difference between patients with chronic asthma and healthy subjects in terms of set shifting, inhibition, and attention performance. This study revealed that the executive functions of patients with chronic asthma have significant defects.


Plasmonic enhancement of visible-light water splitting with Au-TiO2 composite aerogels.
We demonstrate plasmonic enhancement of visible-light-driven splitting of water at three-dimensionally (3D) networked gold-titania (Au-TiO2) aerogels. The sol-gel-derived ultraporous composite nanoarchitecture, which contains 1 to 8.5 wt% Au nanoparticles and titania in the anatase form, retains the high surface area and mesoporosity of unmodified TiO2 aerogels and maintains stable dispersion of the ~5 nm Au guests. A broad surface plasmon resonance (SPR) feature centered at ~550 nm is present for the Au-TiO2 aerogels, but not Au-free TiO2 aerogels, and spans a wide range of the visible spectrum. Gold-derived SPR in Au-TiO2 aerogels cast as films on transparent electrodes drives photoelectrochemical oxidation of aqueous hydroxide and extends the photocatalytic activity of TiO2 from the ultraviolet region to visible wavelengths exceeding 700 nm. Films of Au-TiO2 aerogels in which Au nanoparticles are deposited on pre-formed TiO2 aerogels by a deposition-precipitation method (DP Au/TiO2) also photoelectrochemically oxidize aqueous hydroxide, but less efficiently than 3D Au-TiO2, despite having an essentially identical Au nanoparticle weight fraction and size distribution. For example, 3D Au-TiO2 containing 1 wt% Au is as active as DP Au/TiO2 with 4 wt% Au. The higher photocatalytic activity of 3D Au-TiO2 derives only in part from its ability to retain the surface area and porosity of unmodified TiO2 aerogel. The magnitude of improvement indicates that in the 3D arrangement either a more accessible photoelectrochemical reaction interphase (three-phase boundary) exists or more efficient conversion of excited surface plasmons into charge carriers occurs, thereby amplifying reactivity over DP Au/TiO2. The difference in photocatalytic efficiency between the two forms of Au-TiO2 demonstrates the importance of defining the structure of Au[parallel]TiO2 interfaces within catalytic Au-TiO2 nanoarchitectures.


Fucose-specific lectin of Aspergillus fumigatus: binding properties and effects on immune response stimulation.
Aspergillus fumigatus is the major causative fungus of aspergillosis, and many studies have explored the relationship between A. fumigatus and pathogenicity. In the current study, we focused on a fucose-specific lectin, FleA, as a novel molecule which related to the pathogenicity of A. fumigatus. The disruption of the fleA gene did not lead to clear morphological changes compared to parental strain under several stress conditions in culture, but germination become earlier. In comparison with parental strain, the pathogenicity of disruptant was enhanced in a mouse infection model. The pattern of conidial phagocytosis and adhesion to cultured cells did not explain this enhanced pathogenicity. FleA was reported to contain six conserved fucose-binding sites; the analysis of constructed FleA point mutants revealed nonequivalent contribution of the fucose-binding sites to fucose binding. Based on the immune response induced in the cultured cells upon exposure to wild-type and mutant FleA, we propose a model of the FleA molecule in A. fumigatus infection.


Serial Synchrotron X-Ray Crystallography (SSX).
Prompted by methodological advances in measurements with X-ray free electron lasers, it was realized in the last two years that traditional (or conventional) methods for data collection from crystals of macromolecular specimens can be complemented by synchrotron measurements on microcrystals that would individually not suffice for a complete data set. Measuring, processing, and merging many partial data sets of this kind requires new techniques which have since been implemented at several third-generation synchrotron facilities, and are described here. Among these, we particularly focus on the possibility of in situ measurements combined with in meso crystal preparations and data analysis with the XDS package and auxiliary programs.


Compositional Analysis and Metabolism of Human Milk Oligosaccharides in Infants.
It is a great success that biotechnological means are available today to produce amounts of single human milk oligosaccharides (HMOs) in a purity which allows performing metabolic and functional studies even in humans. As recent data indicate that there is a link between the Lewis blood group and the secretor status of an individual and certain inflammatory diseases, this review will also focus on the metabolic fate of secretor- and Lewis blood group-specific components. We conclude that there is no simple urinary or fecal excretion pattern of HMOs, although the pattern in urine often reflects the mother's secretor/nonsecretor status. However, there are deviations for single HMOs which deserve special attention. In feces, the variation in excretion is much higher than in urine, which may be caused by variations in the infant's intestinal microbiota. A gradual decrease in HMO excretion with time as proposed earlier does not take place as even after 7 months of exclusive breastfeeding often intact HMOs can be detected in feces and urine. In addition, we found that whenever oligosaccharides were detected in feces, LNT, the major core structure of HMOs, was present. Hence, our data do not support speculations that LNT is a preferable source for the microbiota.