Management of compromised first permanent molars in a cohort of UK paediatric patients referred to hospital-based services.
There are diverse opinions among dentists about managing compromised first permanent molars (cFPMs) in children and a perceived lack of guidance to help them evaluate prognosis. To evaluate the current management of cFPM in children referred to a UK hospital centre and to report the severity of the affected teeth. A service evaluation was undertaken, based on case records of medically fit children (6-11 years) referred to for the management of cFPMs. The presence of hypomineralisation, post-eruptive breakdown and the proposed care plans were recorded. Radiographic signs of severity were scored using the ICDAS index (intra/inter-rater kappa 0.96/0.82). From 349 records screened over a 4-month period, 249 met the selection criteria. Almost 81% were planned to have extraction of at least one cFPM, whereas 19.3% were managed without extraction. More than half of the extraction cases (n = 105) had radiographic radiolucencies not exceeding the middle third of dentine in the worst-affected FPM. At the time of extraction, the mean age of the patients was 9.8 years (±0.9). GA was used in 196 (97.5%) cases, and 40.8% had not received previous treatment in any of their cFPMs. Potentially restorable cFPMs in children is, most of the time, in a cohort of UK patients referred for tier 3 services, being managed by timed extractions under general anasethesia.


Sub-second synthesis of silver nanoparticles in 3D printed monolithic multilayered microfluidic chip: Enhanced chemiluminescence sensing predictions via machine learning algorithms.
Futuristic microfluidics will require alternative ways to extend its potential in vast areas by integrating various facets such as automation of different subsystems, multiplexing, incorporation of cyber-physical capabilities, and rapid prototyping. On the rapid prototyping aspect, for the last decade, additive manufacturing (AM) or 3D printing (3DP) has advanced to become an alternative fabrication process for microfluidic devices, enabling industry-level abilities towards mass production. In this context, for the first time, this work demonstrates the fabrication of monolithic multilayer microfluidic devices (MMMD) from planar orientation (1 layer) to nonplanar (4 layers) monolithic microchannels. The developed MMM device was impeccable for synthesizing highly potentialized silver nanoparticles (AgNPs) in <1 s. Moreover, the transport of chemical species with laminar flow simulations was performed on the process along with the thorough characterizations of produced AgNPs, finding the mean AgNPs particle size of around 35 nm without any post-processing requirements. The well-known catalytic activity of AgNPs was leveraged to enhance weak chemiluminescence (CL) sensing signals by >1300 %, increasing CL sensitivity. Further, machine learning (ML) predictive models encouraged to obtain the experimental parameters without human intervention iterations for target-specific applications. The proposed methodology finds the potential to save resources, time, and enables automation with rapid prototyping, providing possibilities for mass fabrications.


A method for small molecule microarray-based screening for the rapid discovery of affinity-based probes.
We describe herein a new method for the high-throughput identification of affinity-based probes (AfBPs) using a small molecule microarray (SMM) approach. A hydroxylethylene-based small molecule library was first generated by solid-phase combinatorial synthesis. The library was tagged with biotin to facilitate immobilization on avidin-coated slides. Preliminary screening with γ-secretase (both the recombinantly purified protein as well as cellular lysates overexpressing the enzyme) was carried out, in order to identify potential small molecule binders, which were subsequently redesigned into AfBPs. Several specific and potent probes for γ-secretase were thus identified through the binding profiles observed on the SMMs. The SMM platform was able to sensitively and conveniently report activity-based binding interactions between aspartic proteases and their small molecule inhibitors. This new approach thus provides a potentially more rapid and efficient method for developing AfBPs using SMMs.


Proposed categorization of pathological states of EBV-associated T/natural killer-cell lymphoproliferative disorder (LPD) in children and young adults: overlap with chronic active EBV infection and infantile fulminant EBV T-LPD.
EBV-associated T/natural killer (NK)-cell lymphoproliferative disorder (EBV-T/NK LPD) of children and young adults is generally referred to with the blanket nosological term of severe chronic active EBV infection (CAEBV). This disease is rare, associated with high morbidity and mortality, and appears to be more prevalent in East Asian countries. But because there is no grading or categorization system for CAEBV, pathologists and clinicians often disagree regarding diagnosis and therapy. EBV-T/NK LPD includes polyclonal, oligoclonal, and monoclonal proliferation of cytotoxic T and/or NK cells. Moreover, a unique disease previously described as infantile fulminant EBV-associated T-LPD has been identified and overlaps with EBV-T/NK LPD. In the present review a clinicopathological categorization of EBV-T/NK LPD is proposed, based on pathological evaluation and molecular data, as follows: (i) category A1, polymorphic LPD without clonal proliferation of EBV-infected cells; (ii) category A2, polymorphic LPD with clonality; (iii) category A3, monomorphic LPD (T-cell or NK cell lymphoma/leukemia) with clonality; and (iv) category B, monomorphic LPD (T-cell lymphoma) with clonality and fulminant course. Categories A1, A2, and A3 possibly constitute a continuous spectrum and together are equivalent to CAEBV. Category B is the exact equivalent of infantile fulminant EBV-associated T-LPD. It is expected that this categorization system will provide a guide for the better understanding of this disorder. This proposal was approved at the third meeting of the Asian Hematopathology Association (Nagoya, 2006).


Impact of Type of Postoperative Complications on Long-Term Survival of Gastric Cancer Patients: Results From a High-Volume Institution in China.
This study aimed to evaluate the impact of postoperative complication and its etiology on long-term survival for gastric cancer (GC) patients with curative resection. From January 2009 to December 2014, a total of 1,667 GC patients who had undergone curative gastrectomy were analyzed. Patients with severe complications (SCs) (Clavien-Dindo grade III or higher complications or those causing a hospital stay of 15 days or longer) were separated into a "complication group." Univariate and multivariate analyses were performed to reveal the relationship between postoperative complications and long-term survival. A 2:1 propensity score matching (PSM) was used to balance baseline parameters between the two groups. SCs were diagnosed in 168 (10.08%) patients, including different etiology: infectious complications (ICs) in 111 (6.66%) and non-infectious complications (NICs) in 71 (4.26%) patients. Multivariate analysis showed that presence of SCs (P=0.001) was an independent prognostic factor for overall survival, and further analysis by complication type demonstrated that the deteriorated overall survival was mainly caused by ICs (P=0.004) rather than NICs (P=0.068). After PSM, patients with SCs (p=0.002) still had a significantly decreased overall survival, and the presence of ICs (P=0.002) rather than NICs (P=0.067) showed a negative impact on long-term survival. Serious complications, particularly of an infectious type, may have a negative impact on overall survival of GC patients. However, additional multicenter prospective studies with larger sample size are required to verify this issue.


Myocardial infarction in singapore: ethnic variation in evidence-based therapy and its association with socioeconomic status, social network size and perceived stress level.
Singapore is a multiethnic Asian country comprising predominantly Chinese, Malays, and Indians. We sought to study the disparities in evidence-based therapy for people from these three ethnic groups who were admitted to hospital with ST-segment elevation myocardial infarction (STEMI). We also examined its association with socioeconomic level and social network size and the influence on psychological stress level. In a prospective study, patients admitted with STEMI were recruited for a questionnaire survey. Relevant demographic and clinical data were collected. A total of 364 patients were recruited and categorised based on ethnicity: Chinese (222 patients), Malays (72 patients), and Indians (70 patients). Malays and Indians were significantly younger than Chinese at the time of presentation with STEMI. Malays had significantly more children than the Chinese and Indians. Malays were in the lowest socioeconomic class, based on education level (P ≤ .02) and residential type (P ≤ .003). Most (87%) patients were treated with primary percutaneous coronary intervention. There were no significant differences between Chinese, Malays, and Indians in accessibility to primary percutaneous coronary intervention, symptom-to-balloon time, door-to-balloon time, and prescription of evidence-based medications. Malays had larger social networks for information support (P ≤ .05) and financial support (P ≤ .04) than Chinese and Indians. There were no significant differences between the three ethnic groups in satisfaction with social support. The perceived stress level was higher among Malays and Indians than Chinese. Although Malays were underprivileged in the socioeconomic level, no significant difference in healthcare disparities were observed among the three ethnic groups. This may be a reflection of the advancement in Singapore's healthcare system. The lower socioeconomic level may also explain the higher perceived stress level in Malays.


Regional anesthesia in the upper extremity.
We have attempted to formulate a guide for surgeons who operate frequently on the hand and upper extremity and who wish to learn how to provide their own local anesthesia. The methods that we have presented are those that work well in our hands and are in frequent use in our practices. We recognize very clearly that there are other methods and that these work well for other surgeons. The method itself is not of great importance (given that it is safe and effective), but the philosophy of learning is. By observation and by practice, the surgeon will gain further mastery of his specialty; we feel strongly that local anesthesia is as much or more a part of surgery than it is of any other specialty. Reading and observation are important. Dissection, whether in the operating room as part of a surgical procedure or in the anatomy laboratory or morgue, is of great benefit in learning the whereabouts and relationships of the nerves that are to be blocked. In the end, however, the surgeon simply must try the various blocks himself on his own patients. Failure is not a calamity; we have tried to emphasize that there are ways to recover with a reasonable degree of grace. The worst calamity is not to learn, not become facile with techniques that are so ideally suited to surgery in the upper extremity.


Acridine-O6-benzylguanine hybrids: Synthesis, DNA binding, MGMT inhibition and antiproliferative activity.
O6-Methylguanine-DNA-methyltransferase (MGMT) is a key DNA repair enzyme involved in chemoresistance to DNA-alkylating anti-cancer drugs such as Temozolomide (TMZ) through direct repair of drug-induced O6-methylguanine residues in DNA. MGMT substrate analogues, such as O6-benzylguanine (BG), efficiently inactivate MGMT in vitro and in cells; however, these drugs failed to reach the clinic due to adverse side effects. Here, we designed hybrid drugs combining a BG residue covalently linked to a DNA-interacting moiety (6-chloro-2-methoxy-9-aminoacridine). Specifically, two series of hybrids, encompassing three compounds each, were obtained by varying the position of the attachment point of BG (N9 of guanine vs. the benzyl group) and the length and nature of the linker. UV/vis absorption and fluorescence data indicate that all six hybrids adopt an intramolecularly stacked conformation in aqueous solutions in a wide range of temperatures. All hybrids interact with double-stranded DNA, as clearly evidenced by spectrophotometric titrations, without intercalation of the acridine ring and do not induce thermal stabilization of the duplex. All hybrids, as well as the reference DNA intercalator (6-chloro-2-methoxy-9-aminoacridine 8), irreversibly inhibit MGMT in vitro with variable efficiency, comparable to that of BG. In a multidrug-resistant glioblastoma cell line T98G, benzyl-linked hybrids 7a-c and the N9-linked hybrid 19b are moderately cytotoxic (GI50 ≥ 15 μM after 96 h), while N9-linked hybrids 19a and 19c are strongly cytotoxic (GI50 = 1-2 μM), similarly to acridine 8 (GI50 = 0.6 μM). Among all compounds, hybrids 19a and 19c, similarly to BG, display synergic cytotoxic effect upon co-treatment with subtoxic doses of TMZ, with combination index (CI) values as low as 0.2-0.3. In agreement with in vitro results, compound 19a inactivates cellular MGMT but, unlike BG, does not induce significant levels of DNA damage, either alone or in combination with TMZ, as indicated by the results of γH2AX immunostaining experiments. Instead, and unlike BG, compound 19a alone induces significant apoptosis of T98G cells, which is not further increased in a combination with TMZ. These results indicate that molecular mechanisms underlying the cytotoxicity of 19a and its combination with TMZ are distinct from that of BG. The strongly synergic properties of this combination represent an interesting therapeutic opportunity in treating TMZ-resistant cancers.


Increasing frequency of tuberculosis among staff in a South African district hospital: impact of the HIV epidemic on the supply side of health care.
To describe the changing frequency of tuberculosis among staff in a South African hospital, and to compare incidence in health workers with that in ancillary staff, the number and type of cases of tuberculosis among staff diagnosed between 1991 and 1996 were ascertained. The incidence rate of tuberculosis among health workers and ancillary staff was compared with the age-specific rate in the community (20-59 years old). In 1991-1992, 2 cases of tuberculosis were diagnosed among hospital staff; but in 1993-1996 there were 20 cases diagnosed (annualized incidence rates 138/100,000 and 690/100,000; P < 0.0001). Of 14 cases tested (64%), 12 (86%) were infected with human immunodeficiency virus (HIV). Most cases (82%) successfully completed treatment, but 4 died (18%). The incidence of tuberculosis amongst health workers (558/100,000 person-years of observation [PYO]) and ancillary staff (445/100,000 PYO) was not significantly different (P = 0.7), but it was lower than the incidence rate among 20-59 years old people in the community (1543/100,000). Tuberculosis has increased amongst hospital staff, secondary to the impact of HIV. The HIV epidemic is having a substantial impact on the health of hospital staff and interventions to counter this are urgently needed.


Gender role incongruency in general surgery applicants.
Deviation of an individual outside of gender normative stereotypes can limit hiring and promotion. The application, interview, and ranking process for medical students pursuing a general surgery residency has multiple opportunities for gender bias to affect an applicant's acceptance. This study examines medical students applying for a top academic general surgery residency and potential bias in perceived gender roles. 269 medical students were interviewed for categorical positions at an academic general surgery residency. Applicants described themselves in one word; adjectives were compiled and categorized as grindstone, ability, communal, or agentic traits. Groups were compared across applicant gender and race. 42% of applicants were women. When comparing gender, men applicants were more likely to use a grindstone/communal adjective (73.2% vs 57.1%, p = 0.006). Men applicants were less likely to identify with an agentic adjective (21% vs 35%). Contrary to gender stereotypes, women general surgery residency applicants tend to self-identify using ability/agentic adjectives more than men applicants. Bias training is important to mitigate the negative consequences of perceived traditional gender role-violation.


Goodness-of-fit tests for the additive risk model with (p > 2)-dimensional time-invariant covariates.
This paper presents methods for checking the goodness-of-fit of the additive risk model with p(> 2)-dimensional time-invariant covariates. The procedures are an extension of Kim and Lee (1996) who developed a test to assess the additive risk assumption for two-sample censored data. We apply the proposed tests to survival data from South Wales nikel refinery workers. Simulation studies are carried out to investigate the performance of the proposed tests for practical sample sizes.


Lung cancer in patients with head and neck cancer. Incidence and long-term survival.
Of the 3,907 cases of primary head and neck or lung cancer diagnosed between 1961 and 1984, 94 patients were identified with a history of cancer at both sites. The total incidence of lung cancer in our head and neck cancer patients was 5.4 percent. Of the 94 patients, 73 had both cancers diagnosed at our institution. These 73 patients were further analyzed. Squamous cell carcinoma accounted for 63 percent of the lung cancers. Twenty of the lung cancers were synchronous and 47 were metachronous after head and neck cancer. Of the synchronous lung cancers, 50 percent were postoperative stage I, whereas only 11 percent of the metachronous cancers were postoperative stage I. The lung cancer survival rate was significantly better for the synchronous cancer group at 5 years (34 percent) than for the metachronous cancer group (5 percent). The better survival rate was evidently due to the greater proportion of early-stage lung lesions. The relatively large number of advanced-stage lung lesions in the metachronous cancer group suggests that aggressive screening of head and neck cancer patients for lung cancer may detect more metachronous lung cancers at an earlier stage and thus improve the survival rate of these patients.


Age-related changes in gait for multi-surface terrain.
The main purpose of this study was to determine the effects of aging on the variability of gait over multi-surface terrain. An additional aim was to compare this variability to walking on solid ground. Ten young adults and 10 older adults walked along a walkway which contained a middle portion with multi-surface terrain. This multi-surface terrain consisted of solid, compliant, rocky, irregular, slippery, and uneven surfaces. We examined the effects of the multi-surface terrain and age on measures of variability including step length, step width, trunk pitch and roll, trunk centre of mass (tCOM) acceleration, and head acceleration. Step, trunk, and head variability were increased on the multi-surface terrain as compared to solid ground for both young and older adults (p<0.05). Older adults demonstrated larger medial-lateral tCOM acceleration RMS (p=0.0004) and trunk roll RMS (p=0.0001) when walking on the multi-surface terrain. In addition, older adults also walked more slowly (p=0.002) and took shorter steps (p=0.003). However, there were no age-related differences in step variability. The results suggest that multi-surface terrain poses a greater challenge to balance reflected by the increased variability, particularly in older adults.


Parkinson's disease: Diagnosis and appreciation of comorbidities.
Parkinson's disease (PD) is a complex neuropsychiatric disorder that manifests with a variety of motor and nonmotor symptoms. Its incidence increases with age. It is important for clinicians to be able to distinguish symptoms of aging and other comorbidities from those of PD. The diagnosis of PD has traditionally been rendered using strict criteria that mainly rely on the cardinal motor symptoms of rest tremor, rigidity, and bradykinesia. However, newer diagnostic criteria proposed by the Movement Disorders Society for diagnosis of PD collectively reflect a greater appreciation for the nonmotor symptoms. The treatment of PD remains symptomatic and the most noticeable improvements have been documented in the motor symptoms. Levodopa remains the gold standard for therapy, however there are now many other potential medical and surgical treatment strategies. Nonmotor symptoms have been shown to affect quality of life more than the motor symptoms. There is ongoing research into symptomatic and disease modifying treatments. Given the multisystem involvement in PD, an interdisciplinary patient-centered approach is recommended by most experts. This chapter addresses first the diagnostic approach and the many geriatric considerations. This is followed by a review of the nonmotor symptoms. Finally, a summary of current treatment strategies in PD is presented along with potential treatment complications.


Ten-year outcomes following laparoscopic and open abdominal radical hysterectomy for "low-risk" early-stage cervical cancer: A propensity-score based analysis.
Accumulating evidence suggested the detrimental effects of adopting minimally invasive surgery in the management of early-stage cervical cancer. However, long-term evidence on the role of minimally invasive radical hysterectomy in "low-risk" patients exists. This is multi-institutional retrospective study comparing minimally invasive and open radical hysterectomy in low-risk early-stage cervical cancer patients. A propensity-score matching algorithm (1:2) was used to allocate patients into the study groups. Kaplan-Meir model was used to estimate 10-year progression-free and overall survival. Charts of 224 "low-risk" patients were retrieved. Overall, 50 patients undergoing radical hysterectomy were matched with 100 patients undergoing open radical hysterectomy. Minimally invasive radical hysterectomy was associated with a longer median operative time (224 (range, 100-310) vs. 184 (range, 150-240) minutes; p < 0.001), lower estimated blood loss (10 (10-100) vs. 200 (100-1000) ml, p < 0.001), and shorter length of hospital stay (3.8 (3-6) vs. 5.1 (4-12); p < 0.001). Surgical approach did not influence the risk of having intra-operative (4% vs. 1%; p = 0.257) and 90-day severe (grade 3+) postoperative complication rates (4% vs. 8%; p = 0.497). Ten-year disease-free survival was similar between groups (94% vs. 95%; p = 0.812; HR:1.195; 95%CI:0.275, 5.18). Ten-year overall survival was similar between groups (98% vs. 96%; p = 0.995; HR:0.994; 95%CI:0.182, 5.424). Our study appears to support emerging evidence suggesting that, for low-risk patients, laparoscopic radical hysterectomy does not result in worse 10-year outcomes compared to the open approach. However, further research is needed and open abdominal radical hysterectomy remains the standard treatment for cervical cancer patients.


The prevalence of functional gastrointestinal disorders in children in Panama: a school-based study.
Functional gastrointestinal disorders (FGIDs) are common in children, but the epidemiology of FGIDs is incompletely understood. Our aim was to perform a population-based study using Rome III criteria to describe the prevalence of FGIDs in children in Panama. We performed a cross-sectional study of children attending three schools in Panama City, Panama. Children with organic medical diseases were excluded. Subjects provided demographic information and completed the Questionnaire on Pediatric Gastrointestinal Symptoms - Rome III Spanish version. A total of 321 subjects (61.1% female, median age 10 years, range 8-14 years) completed our study. A total of 92 subjects (28.7%) met criteria for an FGID. Gender, age and school type did not differ significantly between subjects with and without FGIDs. The most common FGIDs included functional constipation (15.9%), irritable bowel syndrome (5.6%), and functional abdominal pain or functional abdominal pain syndrome (4.0%). Abdominal pain-related FGIDs were present in 12.1%. FGIDs are common in school-aged children in Panama. The prevalence of abdominal pain-related FGIDs in children in Panama is similar to that described in other parts of the world. Further population-based studies utilising Rome III criteria to measure FGID prevalence in children are needed to advance our understanding of the pathogenesis of FGIDs.


Anxiety and depression: Easing the burden in COPD patients.
Anxiety and depression are common comorbidities of COPD. The simple evaluation tools and therapy options described here can help improve patients' quality of life.


Do Regional Analgesia and Peripheral Blocks Still Have a Place in Joint Arthroplasty?
The efficacy of regional anesthesia and peripheral nerve blocks in the management of postoperative pain has resulted in widespread use of this approach in hip and knee arthroplasty. With extensive clinical use, however, the limitations of this approach have become apparent. These limitations include delays for the surgeon, inefficient use of the operating room, muscular weakness, and associated delays in physical therapy. Periarticular injection of anesthetic and analgesic medications appears to offer comparable benefits to nerve blocks in joint arthroplasty without these limitations. The long-acting anesthetic bupivacaine liposome injectable suspension (EXPAREL®, Pacira Pharmaceuticals, Inc), in particular, has been shown to be highly effective in managing postoperative pain and reducing opioid consumption. Consequently, a growing body of data and extensive clinical experience now support replacing nerve blocks with periarticular injections.


Validation of the Fabricated Cast Nylon Head Phantom for Stereotactic Radiosurgery End-to-End Test using Alanine Dosimeter.
Stereotactic radiosurgery (SRS) is an alternative to surgery as it precisely delivers single-large doses to small tumors. Cast nylon is used in phantom due to its computed tomography (CT) number of about 56-95 HU, which is close to that of the soft tissue. Moreover, cast nylon is also more budget-friendly than the commercial phantoms. The aim of this study is to design and validate the fabricated cast nylon head phantom for SRS end-to-end test using an alanine dosimeter. The phantom was designed using cast nylon. It was initially created by a computer numerical control three-axis vertical machining center. Then, the cast nylon phantom was scanned using a CT simulator. Finally, the validation of the fabricated phantom using alanine dosimeter proficiency with four Varian LINAC machines was performed. The fabricated phantom presented a CT number of 85-90 HU. The outcomes of VMAT SRS plans showed percentage dose differences from 0.24 to 1.55, whereas the percentage dose differences in organ at risk (OAR) were 0.09-10.80 due to the low-dose region. The distance between the target (position 2) and the brainstem (position 3) was 0.88 cm. Variation in dose for OAR is higher, which might be due to a high-dose gradient in the area where measurement was being conducted. The fabricated cast nylon end-to-end test head phantom had been suitably designed to image and irradiate during an end-to-end test for SRS using an alanine dosimeter.


Prevention of Dielectric Breakdown of Nanopore Membranes by Charge Neutralization.
To achieve DNA sequencing using a solid-state nanopore, it is necessary to reduce the electric noise current. The noise current can be decreased by reducing the capacitance (C) of the nanopore device. However, we found that an electric-charge difference (ΔQ) between the electrolyte in one chamber and the electrolyte in another chamber occurred. For low capacitance devices, this electric-charge imbalance can lead to unexpectedly high voltage (ΔV = ΔQ/C) which disrupted the membrane when the two electrolytes were independently poured into the chambers. We elucidated the mechanism for the generation of initial defects and established new procedures for preventing the generation of defects by connecting an electric bypass between the chambers.


Thermomucor indicae-seudaticae on human skin.
Thermomucor indicae-seudaticae Subrahmanyam et al. was found for the first time growing as commensal associated with pityriasis versicolor on the skin of a 25-year-old man living in a small village near Pune, Maharastra, India. The clinical observations and morphological characters are presented. A small percentage of zygospores was found to germinate in situ but further stages of development could not be found.


Modeling mucosal dimensions after implantation of a bio-absorbable membrane for surgical root coverage.
The aim of this study was to model alterations of mucosal thickness after implantation of a bio-absorbable membrane for surgical root coverage employing guided tissue regeneration. Periodontal conditions around 31 recession sites in 14 patients were assessed for up to 12 months after surgery. Mucosal thickness was modeled in a multivariate, three-level (occasion, tooth, subject) time series model. The amount of root coverage was studied in a bivariate multilevel model of change and mean recession to avoid mathematic coupling. Predictions of gingival thickness were, at the outset, strongly related to baseline gingival width. At maxillary teeth, gingival thickness at all measurement locations peaked 3 months after surgery with negative relations to baseline gingival width. Thereafter, thickness gradually decreased but remained higher (0.3-0.5 mm, 95% confidence interval 0.05-0.9 mm) than before surgery, while positive correlations with baseline gingival width were re-established. At mandibular teeth, gingival thickness did not change so dramatically, while thickness of lining mucosa underwent similar changes as at maxillary teeth. In contrast to previous publications, modeling change of recession depth and mean recession did not yield better results in deeper sites when applying a bivariate multilevel model that avoids mathematic coupling.


Obesity promotes lipid accumulation in lymph node metastasis of gastric cancer: a retrospective case‒control study.
The connection between obesity, lipid accumulation, and lymph node metastasis (LNM) in gastric cancer (GC) is unclear. The association of body mass index (BMI) and serum lipid levels with LNM was measured by calculating the odds ratio (OR) and 95% confidence interval (CI) in 1,058 eligible GC patients with a mean age of 61.4 years. Meanwhile, differentially expressed genes (DEGs) were identified between lymph node metastasis-positive (N +) and -negative (N0) groups using public RNA-seq data. Neutral lipids in human GC samples were detected by Oil red O staining. The expression of cluster of differentiation 36 (CD36), fatty acid synthase (FASN), and lipoprotein lipase (LPL) was detected by immunohistochemistry (IHC) and quantitative real-time PCR. Compared with normal-weight patients, overweight (OR = 2.02, 95% CI = 1.26-3.23) and obese (OR = 1.83, 95% CI = 1.15-2.91) patients showed increased ORs for LNM. However, no significant results were obtained for serum lipids in the multivariable-adjusted model (P > 0.05). Subgroup analysis suggested that increased low-density lipoprotein cholesterol was a risk factor in females (OR = 1.27, 95% CI = 1.02-1.59). Functional enrichment analysis of DEGs revealed a connection between lipid metabolism and LNM. Meanwhile, lipid staining showed a mass of lipids in obese N + tumor samples, and IHC analysis indicated an increase in LPL and CD36 expression in N + cases, implying a crucial role for exogenous lipid supply in LNM. High BMI significantly increases the risk of LNM in GC and promotes lipid accumulation in GC cells in LNM.


Deciphering the enigmatic crosstalk between prostate cancer and Alzheimer's disease: A current update on molecular mechanisms and combination therapy.
Alzheimer's disease (AD) and prostate cancer (PCa) are considered the leading causes of death in elderly people worldwide. Although both these diseases have striking differences in their pathologies, a few underlying mechanisms are similar when cell survival is considered. In the current study, we employed an in-silico approach to decipher the possible role of bacterial proteins in the initiation and progression of AD and PCa. We further analyzed the molecular connections between these two life-threatening diseases. The androgen deprivation therapy used against PCa has been shown to promote castrate resistant PCa as well as AD. In addition, cell signaling pathways, such as Akt, IGF, and Wnt contribute to the progression of both AD and PCa. Besides, various proteins and genes are also common in disease progression. One such similarity is mTOR signaling. mTOR is the common downstream target for many signaling pathways and plays a vital role in both PCa and AD. Targeting mTOR can be a favorable line of treatment for both AD and PCa. However, drug resistance is one of the challenges in effective drug therapy. A few drugs that target mTOR have now become ineffective due to the development of resistance. In that regard, phytochemicals can be a rich source of novel drug candidates as they can act via multiple mechanisms. This review also presents mTOR targeting phytochemicals with promising anti-PCa, anti-AD activities, and approaches to overcome the issues associated with phytochemical-based therapies in clinical trials.


Association of individual green space exposure with the incidence of asthma and allergic rhinitis: a systematic review and meta-analysis.
The association between allergic respiratory diseases, such as asthma and allergic rhinitis (AR), and green space (GS) remains controversial. Our study aimed to summarize and synthesize the association between individual GS exposure and the incidence of asthma/AR. We systematically summarized the qualitative relationship between GS exposure and asthma and AR. The pooled odds ratio (OR) with 95% confidence intervals (CIs) was used to estimate the effect of the Normalized Difference Vegetation Index (NDVI) on asthma and AR. A total of 21 studies were included for systematic review, and 8 of them underwent meta-analysis. In the meta-analysis of current asthma, the 0 < radius ≤ 100 m group, 100 < radius ≤ 300 m group, and 500 < radius ≤ 1000 m group presented weak negative associations between the NDVI and current asthma. For ever asthma, slight positive associations existed in the 0 < radius ≤ 100 m group and 300 < radius ≤ 500 m group. In addition, the NDVI might slightly reduce the risk of AR in radius of 100 m and 500 m. Our findings suggest that the effects of GS exposure on asthma and AR were not significant. Differences in GS measurements, disease diagnoses and adjusted confounders across studies may have an impact on the results. Subsequent studies should consider potential confounding factors and use more accurate GS exposure measurements to better understand the impact of GS exposure on respiratory disease in the population.


Ophthalmic manifestations of sickle cell disease: update of the latest findings.
Recent developments in the diagnosis and management of sickle cell ocular manifestations are reviewed to enable the clinician to better manage the ophthalmic care of these patients. Research over the past year has focused upon systemic and ocular clues to the presence of sickle cell retinopathy. In addition, newer imaging modalities, such as spectral domain optical coherence tomography and wide-field imaging, have resulted in the detection of subclinical retinopathy related to sickle cell disease. Decreased retinal function (via microperimetry testing) has also been detected in association with areas of retinal thinning. Identification of these ocular and systemic factors that are associated with sickle cell retinopathy will help identify those patients who most need to be screened for sickle cell retinopathy. The awareness of subclinical disease as well as the identification of systemic factors associated with higher prevalence of sickle cell retinopathy will aid the clinician in identifying those patients who are at higher risk of retinopathy.


Determination of the pKa values of beta-blockers by automated potentiometric titrations.
The acid-base equilibrium constants of the beta-blockers atenolol, oxprenolol, timolol and labetalol were determined by automated potentiometric titrations. The pKa values were obtained in water-rich or water methanol medium (20% MeOH) to obviate the solubility problems associated with the compounds. The initial estimates of pKa values were obtained from Gran's method and then, were refined by the NYTIT and ZETA versions of the LETAGROP computer program. The resultant values were 9.4 (I = 0.1 M KCl, 20% methanol) for atenolol, 9.6 (I = 0.1 M KCl) for oxprenolol, 9.4 (I = 0.1 M KCl, 20% methanol) for timolol and 7.4 and 9.4 (I = 0.1 M KCl) for labetalol. The potentiometric method was found to be accurate and easily applicable. The operational criteria for applying the methodology are indicated.


Bifunctional killing activity encoded by conserved reaper proteins.
Drosophila activators of apoptosis mapping to the Reaper region function, in part, by antagonizing IAP proteins through a shared RHG motif. We isolated Reaper from the Blowfly L. cuprina, which triggered extensive apoptosis in Drosophila cells. Conserved regions of Reaper were tested in the context of GFP fusions and a second killing activity, distinct from the RHG, was identified. A 20 amino-acid peptide, designated R3, conferred targeting to a focal compartment and promoted membrane blebbing. Killing by the R3 fragment did not correlate with translational suppression or with reduced DIAP1 levels. Likewise, R3-induced cell deaths were only modestly suppressed by silencing of Dronc and involved no detectable association with DIAP1. Instead, a second IAP-binding domain, distinct from the R3, was identified at the C terminus of Reaper that bound to DIAP1 but failed to trigger apoptosis. Collectively, these findings are inconsistent with single effector models for cell killing by Reaper and suggest, instead, that Reaper encodes conserved bifunctional death activities that propagate through distinct effector pathways.


Treatment and outcome of acquired haemophilia A with a standard conventional regimen in a cohort without associated conditions.
Acquired haemophilia A (AH) is a rare bleeding disorder with significant risk of mortality. We conducted a study on the treatment and outcomes of patients with AH diagnosed between 1998 and 2004 in our institution. Fourteen patients (age range 17-89, median 64) were followed-up from between 10-64 months (average 32 months). Inhibitor levels ranged from 5 to 450 BU. Ten patients required either recombinant activated factor VIIa or prothrombin complexes for control of bleeding. All patients received a standard immunosuppressive regimen of prednisolone 1 mg kg day(-1) and oral cyclophosphamide 50-100 mg day(-1). In addition, nine patients received intravenous immunoglobulin. Complete remission (CR) was achieved in 88% (eight of nine evaluable patients) over durations ranging from 5-78 days (average 35 days). There were three mortality; from bleeding, sepsis and cerebral infarct. Two patients were lost to follow-up. There were no relapses among patients achieving CR. Conditions associated with AH were not identified at diagnosis or subsequent follow-up in all patients. This series represent one of the largest aetiologically and treatment-wise, uniformed cohort of AH patients. Despite toxicity concerns, the combination of prednisolone and cyclophosphamide remain an effective regimen and should be among the first line of treatment choices, with careful patient selection.


Influence of volume reduction and cryopreservation methodologies on quality of thawed umbilical cord blood units for transplantation.
Although there is considerable variability in methodology among umbilical cord blood banks, their common goal is to achieve optimal product quality for transplantation. Cryopreservation is a critical issue for a long-term maintenance of cord blood viability and colony-forming capacities. We designed a prospective study to compare controlled (CRF) vs. non-controlled freezing (URF) of volume-reduced cord blood units. In addition, the influence of hydroxy ethyl starch (HES) on cryopreservation was also assayed. To assess the efficiency of protocols used, cell recoveries were measured and the presence of hematopoietic colony-forming units was quantified. In the study phase, we observed similar CB haematopoietc recoveries for CRF and URF strategies, except for TNC recovery that was better for HES volume reduced CB units in the URF group. When we analysed the data of routine processed CB units in samples from satellite cryovials, we found better BFU-E, CFU-GM, CFU-GEMM and CFU recoveries for those units processed with HES than without HES, in an URF manner. URF of CB units is a cryopreservation procedure that allows similar hematopoietic progenitor recoveries than CRF with programmed devices. However, our study suggests that those banks that cryopreserve CB units in a URF manner should use HES for volume reduction. On the other hand, for CRF cryopreservation methodology volume reduction with and without HES are equally useful.


Overview on vitamin D and sunbed use.
Vitamin D seems to be associated with a protective effect in a vast range of diseases, including cardiovascular, autoimmune and oncologic conditions. Since ultraviolet (UV) B light is the most important prerequisite for the cutaneous synthesis of vitamin D, sunbeds are able to increase serum vitamin D levels, although only transiently in most cases. In this scenario, the artificial tanning industry relentlessly tries to promote the use of sunbeds as a 'safe' therapeutic measure to achieve an adequate serum vitamin D status. The World Health Organization classified UV-emitting tanning devices, as well as the whole UV spectrum, as group-1 carcinogens, as they significantly increase the risk of melanoma and non-melanoma skin cancer. In case of vitamin D deficiency or insufficiency, the current risk-benefit ratio is therefore in favour of vitamin D supplementation instead of sunbed use. Artificial tanning devices should never be considered as an option to achieve an appropriate vitamin D status. Their supposedly beneficial effects, vastly publicised by the artificial tanning industry, are not worth the carcinogenic risk associated with sunbed use.


Expression of MHC class II in T cells is associated with increased HIV-1 expression.
HIV-1 replicates in activated T cells at significantly higher levels than in resting cells. Thus, certain molecules up-regulated during T cell activation appear to be important for HIV-1 replication. In this study, we present evidence suggesting that expression of MHC class II (class II) molecules on CD4+ T cells facilitate HIV-1 replication. T cells that expressed class II supported greater virus replication than T cells lacking class II. The class II+ cells, when either infected with HIV-1 or transfected with an env-minus HIV-1 provirus plasmid, produced 10-20-fold greater virus expression than class II- cells. Anti-class II antibody markedly inhibited virus expression in class II+ cells (but not class II- cells) and also decreased the nuclear binding activity of AP-1, an inducible transcription factor important in T cell activation and HIV-1 expression. Most importantly, the induction of class II expression by transfection of the MHC class II transactivator (CIITA) stimulated HIV-1 replication in Jurkat T cells. Taken together, these data suggest that expression of MHC class II molecules and/or CIITA in T cells enhances HIV-1 transcription.


A climate-based malaria model with the use of bed nets.
Insecticide-treated bed nets (ITNs) are among the most important and effective intervention measures against malaria. In order to investigate the impact of bed net use on disease control, we formulate a periodic vector-bias malaria model incorporating the juvenile stage of mosquitoes and the use of ITNs. We derive the vector reproduction ratio [Formula: see text] and the basic reproduction ratio [Formula: see text]. We show that the global dynamics of the model is completely determined by these two reproduction ratios. More precisely, the mosquito-free periodic solution is globally attractive if [Formula: see text]; the unique disease-free periodic solution is globally attractive if [Formula: see text] and [Formula: see text]; and the model admits a unique positive periodic solution and it is globally attractive if [Formula: see text] and [Formula: see text]. Numerically, we study the malaria transmission case in Port Harcourt, Nigeria. Our findings show that the use of ITNs has a positive effect on reducing [Formula: see text], and that malaria may be eliminated from this area if over 75% of the human population were to use ITNs. The simulation about the long term behavior of solutions has good agreement with the obtained analytic result. Moreover, we find that the ignorance of the vector-bias effect may result in underestimation of the basic reproduction ratio [Formula: see text]. Another notable result is that the infection risk would be underestimated if the basic reproduction ratio [Formula: see text] of the time-averaged autonomous system were used.


Combined use of multiple methodologies for the measurement of total antioxidant capacity in UK commercially available vegetable juices.
Substantial evidence exists to support the hypothesis that high fruit and vegetable consumption, rich in antioxidants, can reduce the incidence of several disease states. The aim of this study was to compare the results obtained by six spectrophotometric biochemical methods including the ferric reducing antioxidant power (FRAP), 2, 2-diphenyl-1-picryhydrazyl (DPPH•), 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS•⁺), copper (II) reducing capacity (CUPRAC) and Cerium (IV) reducing antioxidant capacity (CERAC) assays as well as Folin-Ciocalteu method (FC) for the measurement of total antioxidant capacity (TAC) and total polyphenols (TP) in different commercially available vegetable juices. There was a significant positive correlation between the results obtained for FRAP, ABTS•⁺, CUPRAC, CERAC and FC (0.68 ≤ r ≤ 0.96, P < 0.01). DPPH• was only correlated with CERAC (r = 0.66, P < 0.01). Beetroot juice had the highest TAC and TP regardless of the method of analysis.


Association Between Prenatal Exposure to Metals and Atopic Dermatitis Among Children Aged 4 Years in Taiwan.
The prevalence of atopic dermatitis has substantially increased in recent decades, and atopic dermatitis could lead to allergic airway inflammation later in life. A previous study found that inorganic arsenic exposure was associated with allergic airway inflammation in children aged 8 to 14 years. However, the association between prenatal exposure to arsenic and other metals and the risk of atopic dermatitis among young children remains unknown. To assess the association between prenatal exposure to arsenic and other metals and the occurrence of atopic dermatitis in children at age 4 years. In total, 1152 pregnant women were enrolled in the original Taiwan Maternal and Infant Cohort Study (TMICS), a multicenter birth cohort study conducted at 9 hospitals in northern, central, southern, and eastern Taiwan from October 2012 to May 2015. Of those, 586 mothers and children aged 4 years participated in follow-up questionnaire interviews from August 2016 to January 2019. After excluding 216 participants with missing data, the final statistical analysis of follow-up data included 370 mother and child pairs from the central and eastern regions of Taiwan. Data were analyzed from February 2 to August 12, 2021. Arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc during pregnancy. The outcome was parent-reported atopic dermatitis history among children aged 4 years. The presence of atopic dermatitis was defined as a positive response to the question, "Has your child ever had atopic dermatitis diagnosed by a physician?" During the initial TMICS study period, concentrations of arsenic, cadmium, lead, cobalt, copper, nickel, thallium, and zinc were measured in maternal urine during the third trimester of pregnancy using an inductively coupled plasma mass spectrometer. Estimated total inorganic arsenic exposure was calculated using a model that included data on both total arsenic and arsenic species (arsenite, arsenate, monomethylarsonate, and dimethylarsenate) obtained from a previous TMICS cohort. Among 370 children included in the analysis, the mean (SD) age was 3.94 (0.59) years; 208 children (56.2%) were male, and 267 children (72.2%) were from the central region of Taiwan. A total of 110 children (29.7%) had atopic dermatitis at age 4 years. Maternal estimated total inorganic arsenic exposure during pregnancy was associated with increased odds of atopic dermatitis among children at age 4 years (odds ratio [OR], 2.42 [95% CI, 1.33-4.39] for every doubled increase of total inorganic arsenic) after adjusting for parental allergies, child's sex, geographic area, maternal educational level, and exposure to tobacco smoke. Every increased unit in the weighted quantile sum index of maternal metal exposure was significantly associated with atopic dermatitis (OR, 1.63; 95% CI, 1.28-2.07). Arsenic (40.1%) and cadmium (20.5%) accounted for most of the metal mixture index. This cohort study found that prenatal exposure to inorganic arsenic and coexposure to inorganic arsenic and cadmium were associated with a higher risk of atopic dermatitis in young children. These findings suggest that prevention of exposure to inorganic arsenic and cadmium during pregnancy may be helpful for the control of atopic dermatitis and other potential allergies in children.


The effect of fiscal decentralization, environmental regulation, and economic development on haze pollution: empirical evidence for 270 Chinese cities during 2007-2016.
The current discourse addresses fiscal issues, financial decentralization, and environmental quality and significantly affects economic development and sustainability. This investigation aims to address the research gap in fiscal decentralization and haze pollution for innovation and sustainable growth. This study uses the annual data of 270 Chinese cities from 2007 to 2016 for comprehensive analysis and employs spatial regression methods. The key findings imply that haze pollution in neighbouring cities causes further ecological issues. While the environmental regulations of China tend to have negative impacts on pollution, fiscal decentralization was found to be a key contributor to environmental pollution in Chinese cities. Overall, the study supports the validity of the pollution refuge hypothesis in China. Lastly, the conclusions allow us to conclude that China might need micro-level reforms regarding fiscal decentralization, environmental tax laws, and encouragement of cleaner production technologies.


Isolated bioinductive repair of partial-thickness rotator cuff tears using a resorbable bovine collagen implant: two-year radiologic and clinical outcomes from a prospective multicenter study.
Current surgical treatment options for partial-thickness tears (eg, takedown and repair, in situ repair) are limited by the degenerative nature of the underlying tendon and may require extensive intervention that can alter the anatomic footprint. The complexity of available techniques to address these issues led to the development of a resorbable collagen implant, which can be used to create a bioinductive repair of partial-thickness tears. We prospectively enrolled 33 patients with chronic, degenerative, intermediate-grade (n = 12), or high-grade (n = 21) partial-thickness tears (11 articular, 10 bursal, 4 intrasubstance, and 8 hybrid) of the supraspinatus tendon in a multicenter study. After arthroscopic subacromial decompression without a traditional rotator cuff repair, a bioinductive implant was secured over the bursal surface of the tendon. Clinical outcomes were assessed using American Shoulder and Elbow Surgeons (ASES) and Constant-Murley scores (CMS) preoperatively and at 3 months, 1 year, and 2 years postoperatively. Magnetic resonance imaging was performed to assess postoperative tendon healing and thickness at the original tear site. At 2-year follow-up, mean ASES and CMS scores improved both clinically and statistically at 1 and 2 years, compared with baseline, for intermediate- and high-grade tears. There was magnetic resonance imaging evidence of new tissue fill-in within the original baseline tear in 100% of the intermediate-grade tears and 95% of the high-grade tears. In 90.9% of the intermediate-grade tears and 84.2% of the high-grade tears, this new tissue fill-in represented at least an additional 50% of the volume of the initial lesion. From baseline to 2-year follow-up, the mean tendon thickness increased by 1.2 mm (standard deviation, 1.3; P = .012) and 1.8 mm (standard deviation, 2.2; P = .003) in the intermediate- and high-grade tears, respectively. The analysis of tear grade and location revealed no statistically significant difference in the change in mean tendon thickness at any time point. One patient with a high-grade articular lesion demonstrated progression to a full-thickness tear; however, the patient was noncompliant and the injury occurred while shoveling snow 1 month after surgery. Neither tear location nor treatment of bicep pathology affected the ASES or CMS scores at any follow-up point. No serious adverse events related to the implant were reported. Final results from this 2-year prospective study indicate that the use of this resorbable bovine collagen implant for isolated bioinductive repair of intermediate- and high-grade partial-thickness rotator cuff tears of the supraspinatus is safe and effective, regardless of tear grade and location.


Platelet-rich plasma for osteoarthritis treatment.
We conducted a comprehensive and systematic search of the literature on the use of platelet-rich plasma (PRP) in the treatment of osteoarthritis, using the Medline, Lilacs, Cochrane and SciELO databases, from May 2012 to October 2013. A total of 23 studies were selected, with nine being controlled trials and, of these, seven randomized, which included 725 patients. In this series, the group receiving PRP showed improvement in pain and joint function compared to placebo and hyaluronic acid. The response lasted up to two years and was better in milder cases. However it was found that there is no standardization in the PRP production method, neither in the number, timing, and volume of applications. Furthermore, the populations studied were not clearly described in many studies. Thus, these results should be analyzed with caution, and further studies with more standardized methods would be necessary for a more consistent conclusion about the PRP role in osteoarthritis.


A dual-responsive crimson fluorescent probe for real-time diagnosis of alcoholic acute liver injury.
The polarity and viscosity of the microenvironment are associated with the control of the onset and progression of pathological diseases, including inflammation, immuno-suppression and cancer. If appropriate treatment is neglected, alcoholic acute liver injury (AALI), the initial sign of alcoholic liver diseases, may transform into hepatic lesions. Therefore, it's crucial to create a particular probe to detect AALI swiftly and track its progression. Herein a polarity and viscosity dual-responsive crimson fluorescent probe (PPBI) was designed and developed, which can target mitochondria and lipid droplets. PPBI possesses aggregation-induced emission properties, good photostability and strong anti-interference ability against pH, metal ions, anions and biomolecules. This probe can distinguish cancer cells from normal ones using changes of green and red fluorescence, as well as identify changes in the cellular microenvironment associated with inflammatory and ferroptosis processes. In addition, changes in polarity and viscosity can be amplified by in vivo imaging in a mouse model to monitor alcohol-induced acute liver injury and to effectively detect the course of pharmacological intervention therapy. All the results suggest that PPBI could be a promising real-time fluorescence imaging tool for diagnosis and treatment of acute alcoholic liver injury.


Autoreactive epitopes within the human alpha-enolase and their recognition by sera from patients with endometriosis.
Patients with endometriosis significantly develop autoantibodies directed against endometrial proteins, which may be involved in the aetiology of this gynaecological disease. Based on standard Western blot analysis, a 48 kDa protein was localized in the soluble protein extract of endometrial adenocarcinoma cells using sera from patients with clinically staged endometriosis and identified as the glycolytic enzyme alpha-enolase. The corresponding cDNA coding for the human alpha-enolase was isolated from a human endometrial cDNA library and cloned into the vector pH6EX3, allowing the efficient expression of recombinant human alpha-enolase with an N-terminal histidine-hexapeptide as affinity ligand in Escherichia coli. The purified recombinant human alpha-enolase was evaluated as a specific antigenic tool for the diagnostic measurement of antiendometrial antibodies in sera from patients with endometriosis. With selected endometriosis sera, two linear autoreactive epitopes were localized within the recombinant human alpha-enolase using epitope mapping techniques, and they were characterized.


Brevundimonas diminuta isolated from mines polluted soil immobilized cadmium (Cd2+) and zinc (Zn2+) through calcium carbonate precipitation: Microscopic and spectroscopic investigations.
The toxic metal(loid)s TMs resistant bacterium Brevundimonas diminuta was isolated for the first time from mines polluted soil in Fengxian, China, and assessed for its potential for Cd and Zn precipitation in Cd and Zn co-contaminated aqueous solution at various Cd and Zn levels (20, 40, 80, 160, and 200 mg L-1), pH values (5, 6, 7, 8, and 9), and temperatures (20, 25, 30, and 35 °C). B. diminuta showed a high resistance to both Cd and Zn and was able to precipitate up to 99.2 and 99.7% of dissolved Cd and Zn respectively, at a pH of 7 and temperature of 30 °C. B. diminuta reduced the dissolved concentrations of Cd and Zn below the threshold levels in water. The 3D-EEM analysis revealed the presence of extracellular polymeric substances (EPS) such as tryptophan indicating bacterial growth under Cd/Zn stress. FTIR showed polysaccharides, CO32-, CaCO3, PO43-, and proteins, which may enhance bacterial growth and metal precipitation. SEM-EDS confirmed the leaf-like and granular shape of the biological precipitation and reduction in the percent weight of TMs, which promoted the adhesion/adsorption of Cd2+, Zn2+, and Ca2+. Moreover, XRD analysis confirmed the precipitation of Cd, Zn, and Ca in the form of CdCO3/Cd3(PO4)2, ZnCO3/ZnHPO4/Zn2(OH)PO4/Zn3(PO4)2, and CaCO3/Ca5(PO3)4OH, respectively. These findings indicate that Brevundimonas diminuta can be used for the bioremediation of TMs-contaminated aquatic environments.


Characterization of In111, a class 1 integron that carries the extended-spectrum beta-lactamase gene blaIBC-1.
A class 1 integron, In111, carried by a self-transferable plasmid from an Escherichia coli clinical strain was characterized. The variable region of In111 constituted an array of gene cassettes encoding the extended-spectrum beta-lactamase IBC-1, the aminoglycoside-modifying enzymes AAC(6')-Ib and ANT(3")-Ia, dihydrofolate reductase I and a putative polypeptide (SMR-2) sharing similarity with the Qac transporters. Transcription of the gene cassettes was driven by a hybrid-type P1 promoter located in a typical 5' conserved segment (CS). The 3'CS included sulI, qacEDelta1, orf5 and orf6. In111 was bounded on the right by an inversely oriented IRt. The 5'CS was preceded by an intact IS26 element followed by an aphA1 gene.


Benefits of hand massage on anxiety in preoperative outpatient: A quasi-experimental study with pre- and post-tests.
Surgical patients experience procedure-related anxiety preoperatively. With delays and long waiting periods, surgical patients can experience increased anxiety and decreased satisfaction with their hospital visit. To evaluate whether a 15-minute non-therapeutic hand massage provided by the Caring Hands massage volunteers would reduce anxiety levels, increase satisfaction, and decrease physiological parameters among preoperative surgical patients. This research study has a quasi-experimental design, with control and intervention groups, and pre and post-tests. This research study was conducted at Same Day Surgical Stations 53 and 63 at the Mayo Clinic Hospital, Methodist Campus, in Rochester Minnesota. One hundred and thirty-eight surgical outpatients were recruited preoperatively, with 31 participants in the control group and 107 in the intervention group. Patients in the control group were asked to rest for 15 min. Patients in the intervention group received a 15-minute non-therapeutic hand massage administered by the Caring Hands massage volunteers from the Mayo Clinic Volunteer Program. Patient anxiety level and physiological parameters were measured and recorded before and after a resting session (control group) or a 15-minute non-therapeutic hand massage session (intervention group). Patients in the intervention group were also surveyed for satisfaction. The feasibility of incorporating a 15-minute non-therapeutic hand massage into the preoperative routine was also analyzed. After receiving a 15-minute non-therapeutic hand massage, patients experienced reduced anxiety levels and increased satisfaction. It was also found that it is feasible to add a 15-minute non-therapeutic hand massage to the routine of a same-day surgical station.


Fast differential interference contrast imaging combined with autocorrelation treatments to measure the heart rate of embryonic fish.
To develop an accurate and convenient method for measuring the heart rate of zebra fish in vivo, a system combining fast differential interference contrast (DIC) imaging with an autocorrelation technique is established. The imaging correlation coefficient corr(i,j) between frame i, selected from the obtained time-lapse imaging series as the reference image, and any other frame j, is calculated as the time-dependent cycle course. Heat rate is determined by the cycle period of the corr with a high temporal resolution of 4 ms, achieved by fast charge-coupled device (CCD) imaging of 250 frames per second. With this high-resolution system, we find that 1-mgL cadmium not only induces the slowing of the heart rate, but also caused signs of arrhythmia in treated fish.


Reduced prefrontal cortical dopamine, but not acetylcholine, release in vivo after repeated, intermittent phencyclidine administration to rats.
Subchronic administration of phencyclidine to rats or monkeys produces prefrontal cortical cognitive dysfunction, as well as reduced frontal cortical dopamine utilization. In the current study, the effects of subchronic exposure to phencyclidine on dopamine and acetylcholine release in the prefrontal cortex were assessed, using in vivo microdialysis in conscious rats. Subchronic exposure to phencyclidine (5 mg/kg twice daily for 7 days) reduced both basal extracellular concentrations of dopamine as well as the increase in dopamine release produced by an acute phencyclidine challenge. The increase in dopamine release induced by a high potassium concentration in the perfusate tended to be reduced after subchronic phencyclidine treatment, while basal and evoked acetylcholine release was unaffected. These data demonstrate that altered dopamine turnover in subjects after subchronic exposure to phencyclidine is directly reflective of reduced release, and as such, represents a functionally relevant phenomenon.


Bladder filling attenuates spinal cord nociceptive reflexes in humans.
To examine the viscerosomatic interaction between bladder afferents and somatic nociception we evaluated the effect of bladder filling on the nociceptive withdrawal reflex (NWR) in 21 healthy subjects. NWR was evoked in the lower and upper limbs by stimulating the sural and index finger digital nerves, respectively, while simultaneously recording EMG activity in the biceps femoris and biceps brachialis. NWR pain-related perception was quantified on a 10-point pain scale. Bladder filling was evaluated with suprapubic bladder sonography. Subjects were examined during empty bladder, medium and high level of bladder filling sessions. NWR magnitude in both upper and lower limbs and perceived pain for the upper limb were significantly decreased at higher levels of bladder filling compared to empty bladder sessions. Reduced NWR magnitude in both upper and lower limbs during bladder filling strongly indicates that bladder control and nociception share common modulatory descending pathways. Bladder afferents may activate these pathways to suppress the micturition reflex, but they may also inhibit spinal reflexes to maintain continence during pain stimuli. The effect of bladder filling on the NWR may represent a useful tool to investigate interactions between the neural pathways controlling the bladder and pain.


Sixth nerve palsy in sporadic Burkitt Lymphoma.
To describe a unique presentation of Central Nervous System Burkitt Lymphoma. A 59-year-old male presented with new onset binocular horizontal diplopia five days after initial presentation with abdominal distension, weight loss, and night sweats. He was diagnosed with Burkitt Lymphoma with base of skull metastasis that was initially visible only on PET scan and subsequently resolved with chemotherapy. Burkitt Lymphoma (BL) is an aggressive type of B-cell, non-Hodgkin, lymphoma that arises due to a translocation of the MYC proto-oncogene. Although central nervous system (CNS) involvement has been described previously with BL, isolated sixth nerve palsy as the initial sign of CNS metastasis is rare. Suspicion should remain high for metastatic disease in patients presenting with acute-onset neurologic complaints even when initial imaging is negative as timely treatment can prevent poor outcomes.


[Clinical study on effect of quyu xiaoban capsule on regression of atherosclerosis].
To study the effect of Quyu Xiaoban capsule (QXC) on regression and stabilization of atherosclerotic plaque with high-frequency ultrasound technique. Eighty patients with atherosclerosis (AS) were randomly divided into the treated group and the control group, level of blood lipids was measured, and intima-media thickness (IMT) and corrected value of image average echo intensity (AIIc%) were determined by ultrasound technique at the beginning of experiment and after being treated for six months. The levels of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) were significantly decreased in the treated group after treatment (68.12 +/- 5.54 vs 61.43 +/- 5.37, P<0.05). The AIIc% of fatty atherosclerotic plaque was significantly increased after treatment (68.12 +/- 5.54 vs 61.43 +/- 5.37), and the change rate of AIIc% in the treated group was significantly different to that in the control group (10.9 +/- 5.1% vs 2.5 +/- 5.5%, P < 0.05). QXC can significantly lower the blood lipids level, delay the progress and enhance the stability of atherosclerotic plaque.


[Effectiveness of nutritional support of elderly and senile of orthopedic traumatological profile].
An analysis of results of the operative treatment of 36 patients who received and did not receive nutritional support in the pre- and postoperative periods has shown that the nutritional support improves the course of the postoperative period.


Pulmonary complications following hematopoietic stem cell transplantation: diagnostic approaches.
Pulmonary complications are a significant cause of morbidity and mortality in hematopoietic stem cell transplant recipients. Pulmonary infiltrates in such patients pose a major challenge for clinicians because of the wide differential diagnosis of infectious and noninfectious conditions. It is rare for the diagnosis to be made by chest radiograph, and commonly these patients will need further invasive and noninvasive studies to confirm the etiology of the pulmonary infiltrates. This review describes the role of the different diagnostic tools available to reach a diagnosis in a timely manner in this patient population.


A robust GC-MS method for the quantitation of fatty acids in biological systems.
Fatty acids (FAs) are involved in a wide range of functions in biological systems. It is important to measure the exact amount of fatty acids in biological matrices in order to determine the level of fatty acids and understand the role they play. The ability to quantify fatty acids in various systems, especially plant species and microbes has recently paved the way to the mass production of pharmaceuticals and energy substitutes including biodiesel. This chapter describes an efficient method to quantify the total fatty acids (TFAs) in biological systems using gas chromatography-mass spectrometry (GC-MS) and a commercially available standard mix of fatty acid methyl esters (FAMEs) using a step-by-step methodology to setup a quantitation method using the Agilent Chemstation software.


Hypothesis: a novel route for immortalization of epithelial cells by Epstein-Barr virus.
Transfection of primate tissue explants with a specific sub-fragment (p31) of EBV DNA results in epithelial (but no other) cells proliferating indefinitely (becoming 'immortalized') without evidence of a 'growth crisis'. Molecular evidence supports integration of viral information into the host chromosome, and an early genotypic alteration involving specific amplification of a sub-component (IR1) of p31 DNA, followed by apparent loss of viral DNA from chromosomes, consistent with a 'hit and run' mechanism. However, analysis at the individual cell level during long-term culture, by FISH techniques, reveals chromosomal alterations, and viral sequences surviving within double minute (DM) bodies. Changing growth patterns occurring at different stages during propagation (>a year in culture) may be explained by sporadic reintegration of surviving viral DNA into the host chromosome. Notably, throughout culture, telomere lengths in chromosomal DNAs do not alter but rather retain the length observed in the primary cell populations. Introduction of a growth stimulating function of EBV, BARF1, into the immortalized, non-clonable epithelial cells under conditions which permit overexpression, allows clonal populations to be derived. Based on the data, mechanisms of immortalization, in the absence of a proven viral oncogene in p31 DNA, and possible genes involved, are considered.


The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature.
Cutaneous squamous cell carcinoma (cSCC) has a high tumour mutational burden (50 mutations per megabase DNA pair). Here, we combine whole-exome analyses from 40 primary cSCC tumours, comprising 20 well-differentiated and 20 moderately/poorly differentiated tumours, with accompanying clinical data from a longitudinal study of immunosuppressed and immunocompetent patients and integrate this analysis with independent gene expression studies. We identify commonly mutated genes, copy number changes and altered pathways and processes. Comparisons with tumour differentiation status suggest events which may drive disease progression. Mutational signature analysis reveals the presence of a novel signature (signature 32), whose incidence correlates with chronic exposure to the immunosuppressive drug azathioprine. Characterisation of a panel of 15 cSCC tumour-derived cell lines reveals that they accurately reflect the mutational signatures and genomic alterations of primary tumours and provide a valuable resource for the validation of tumour drivers and therapeutic targets.


An ex vivo angiogenesis assay utilizing commercial porcine carotid artery: modification of the rat aortic ring assay.
The study of angiogenesis as a therapeutic target requires a reliable, physiologically relevant, and technically straightforward assay. An ex vivo assay bridges the gap between cell-based assays, which may not realistically represent the complex process of vessel sprouting, and in vivo assays, which are time consuming and expensive. Porcine carotid arteries provide an ideal tissue source for angiogenesis inhibitor screens due to their availability, physiological relevance and large size. 1.5 mm2 fragments of porcine carotid arteries were incubated in 48-well culture plates and sandwiched between two 100 microliters layers of Matrigel. Sprouting was observed from the explants and quantitated, using a digital imaging system, after two weeks of incubation. Histological analysis using Factor VIII-related antigen (von Willebrand Factor) as an endothelial cell-specific marker identified these sprouts, which were consistent with endothelial cell morphology, supporting the system as a model of angiogenesis. Accordingly, the angiogenesis inhibitors suramin, 2-methoxyestradiol, and the matrix metalloprotease inhibitor Batimastat were shown to completely inhibit sprouting at 50, 0.5, and 5.0 micrograms/ml, respectively and to have ED50 values of 23, 0.15, and 0.14 microgram/ml. This assay shows good reproducibility and eliminates animal to animal variation. The system should prove adaptable to other forms of angiogenic stimulation, ultimately making a variety of assays for angiogenesis available to laboratories of limited resources.


COX-2 Inhibition mediated anti-angiogenic activatable prodrug potentiates cancer therapy in preclinical models.
Anti-angiogenesis, i.e., blocking the angiogenic pathway, has been considered as an important component in current cancer therapeutic modalities. However, the associated benefits have proven to be modest as tumor angiogenesis and regrowth persist, probably due to other ill-defined complex angiogenic mechanisms. Herein, we developed an indomethacin (IMC) incorporating system to mediate hypoxia responsive prodrug (TA) and diagnostic agent (DA) in cancer theranostic applications. Cyclooxygenase 2 (COX-2) elevated expression in several cancer types is closely associated with severe tumor supporting vascularization factors. Our strategy utilizing COX-2 inhibition augmented the anti-angiogenetic induced hypoxia responsive prodrug activation well. Both in vitro and in vivo results proved that DA and TA exhibited specificity towards COX-2 positive (+ve) HeLa and A549 cancer cell lines and activation under hypoxic conditions. Compared with controls (R1, and anticancer drug SN-38), TA displayed prolonged tumor retention and enhanced therapeutic efficacy in xenograft mouse models at a reduced dosage. Our results significantly highlighted the importance of COX-2 blockade mediated anti-angiogenesis in complementing the hypoxia-responsive drug delivery systems (DDSs) and could to beneficial for the rapid development of more efficacious antitumor therapeutics.


Relationships between shape and size of the osteoblasts and the accretion rate of trabecular bone surfaces.
The structure of the osteoblastic layer on trabecular bone surfaces showing different accretion rates was examined. Volume and secretory surface of the cells and thickness of the underlying osteoid border were measured within serial sections. Shape, size and arrangement of osteoblasts varied greatly on the different trabeculae examined, but were relatively homogeneous over each surface. A correlation was found between the volume-secretory surface ration (i.e. the relative amount of protoplasmatic volume involved in osteoid production) and the thickness of the underlying osteoid seam measured separately for each osteoblast.


In vivo evaluation of [(123)I]MNI-420: a novel single photon emission computed tomography radiotracer for imaging of adenosine 2A receptors in brain.
Dysregulation of adenosine 2A (A2A) receptor function in brain has been implicated in multiple psychiatric and neurodegenerative disorders, including schizophrenia and Parkinson's disease, making the development of an imaging agent to study A2A receptors in both healthy brain and disease states desirable. In this study, [(123)I]MNI-420 was evaluated as a potential single photon emission computed tomography (SPECT) radiotracer for imaging A2A receptors in brain. Two adult male monkeys (Macaca fascicularis) and three adult female baboons (Papio anubis) were anesthetized and imaged on Neurofocus SPECT cameras. Baboons underwent baseline and displacement studies using varying doses of caffeine (2.0-20mg/kg). Baseline and pre-blocking experiments with multiple doses of preladenant (0.01-1.2mg/kg), a highly selective A2A antagonist, were performed in cynomolgus monkeys. Following bolus intravenous (i.v.) injection, [(123)I]MNI-420 rapidly entered the non-human primate brain. The regional brain accumulation of [(123)I]MNI-420 matched the known distribution of A2A receptors in brain (highest in the striatum). Striatum to cerebellum ratios and binding potentials of around 3.0-3.5 and 2.0-2.5, respectively, were measured in monkey and baboon brain. A dose-dependent occupancy was observed following i.v. injection of caffeine at pseudo-equilibrium conditions during displacement experiments. Pre-treatment with preladenant blocked specific binding in A2A rich regions in a dose-dependent fashion. The data indicate that [(123)I]MNI-420 holds promise as a SPECT radiotracer for imaging A2A receptors in brain and further evaluation is warranted, in order to determine its utility as a SPECT radiotracer for imaging of A2A in brain.


Coarctation of the thoraco-abdominal aorta associated with mucopolysaccharidosis VII in a child.
Herein we describe a case of atypical coarctation of the thoraco-abdominal aorta associated with mucopolysaccharidosis VII in a 4-year-old girl. Aortography showed diffuse narrowing of the descending aorta. An extra-anatomic bypass was constructed using an 8-mm Dacron graft (Meadox Medicals Inc, Oakland, NJ) between the proximal and distal portion of the descending aorta. Balloon angioplasty was necessary to treat stenoses in the infrarenal abdominal aorta. Two years postoperatively at age 6, aortography revealed no stenosis at the anastomotic sites or in the prosthesis, but the hypoplastic segment of the descending aorta between the anstomoses was completely occluded.


Transfection and Thermotolerance Methods for Analysis of miR-570 Targeting the HSP Chaperone Network.
Heat shock proteins (HSPs) are key stress proteins induced in cells exposed to proteotoxic insult and are critical for thermotolerance. The dynamic network of chaperone interactions, known as the chaperome, contributes significantly to the proteotoxic cell response and the malignant phenotype in cancer. We identified a potent microRNA, miR-570 that could bind the 3'untranslated regions of multiple HSP mRNAs and inhibit HSP synthesis. Here, we will introduce the transfection and thermotolerance methods for analysis of miR-570 targeting the HSP chaperone network.


miRNA-200c-3p targets talin-1 to regulate integrin-mediated cell adhesion.
The ability of integrins on the cell surface to mediate cell adhesion to the extracellular matrix ligands is regulated by intracellular signaling cascades. During this signaling process, the talin (TLN) recruited to integrin cytoplasmic tails plays the critical role of the major adaptor protein to trigger integrin activation. Thus, intracellular levels of TLN are thought to determine integrin-mediated cellular functions. However, the epigenetic regulation of TLN expression and consequent modulation of integrin activation remain to be elucidated. Bioinformatics analysis led us to consider miR-200c-3p as a TLN1-targeting miRNA. To test this, we have generated miR-200c-3p-overexpressing and miR-200c-3p-underexpressing cell lines, including HEK293T, HCT116, and LNCaP cells. Overexpression of miR-200c-3p resulted in a remarkable decrease in the expression of TLN1, which was associated with the suppression of integrin-mediated cell adhesion to fibronectin. In contrast, the reduction in endogenous miR-200c-3p levels led to increased expression of TLN1 and enhanced cell adhesion to fibronectin and focal adhesion plaques formation. Moreover, miR-200c-3p was found to target TLN1 by binding to its 3'-untranslated region (UTR). Taken together, our data indicate that miR-200c-3p contributes to the regulation of integrin activation and cell adhesion via the targeting of TLN1.


The nucleotide sequence of the transforming HindIII-G fragment of adenovirus type 5 DNA. The region between map positions 4.5 (HpaI site) and 8.0 (HindIII site).
The nucleotide sequence of the region between map positions 4.5 (HpaI-site) and 8.0 (HindIII-site) of adenovirus type 5 (Ad5) DNA has been determined. This stretch of DNA is part of the transforming HindIII-G fragment, which is 2809 nucleotides long. The sequenced segment was found to have a long open reading frame for protein biosynthesis, starting 23 nucleotides from the HpaI site and extending all the way to the HindIII-G site, which could code for a protein of at least 44 000 daltons. The possible correlation beteen the coding capacity of the HindIII-G fragment and the "transforming" proteins specified by it will be discussed in the light of the recent data on the splicing of early mRNAs.


Urinary incontinence in children: botulinum toxin is a safe and effective treatment option.
This study's aim was to assess the use of intravesical injection of botulinum neurotoxin type A (BoNT-A) as a treatment of overactive bladder (OAB) in children. A 6-year retrospective study of children who received BoNT-A for OAB was performed. Treatment outcome was classified as complete success (CS), partial success (PS) or treatment failure (TF). Of the 57 patients who received BoNT-A treatment for OAB, 35 were males. CS occurred in 74.2% of males and 54.5% of females. PS was achieved in 20% of males and 18.2% of females. TF occurred in 2.9% of males and 22.7% of females. Anticholinergics had previously been used and had been effective in 58.6% and 83.3% of males and females. Significant side effects to medications were experienced in 12 (41.4%) males and 4 (22.2%) females. Of these, BoNT-A achieved CS in seven (53.3%) males and two (50%) females and PS in three (25%) males and one (25%) female. BoNT-A was successful in seven (58.3%) males and two (66.7%) females where anticholinergics were ineffective. BoNT-A has a role in a carefully selected subgroup of children with overactive bladder symptoms including those with medication side effects and treatment compliance issues. It may have a role in patients who do not respond to conventional therapy.


Predictors for timely initiation of breastfeeding after birth in the hospitals of Nepal- a prospective observational study.
Timely initiation of breastfeeding can reduce neonatal morbidities and mortality. We aimed to study predictors for timely initiation of breastfeeding (within 1 h of birth) among neonates born in hospitals of Nepal. A prospective observational study was conducted in four public hospitals between July and October 2018. All women admitted in the hospital for childbirth and who consented were included in the study. An independent researchers observed whether the neonates were placed in skin-to-skin contact, delay cord clamping and timely initiation of breastfeeding. Sociodemographic variables, obstetric and neonate information were extracted from the maternity register. We analysed predictors for timely initiation of breastfeeding with Pearson chi-square test and multivariate logistic regression. Among the 6488 woman-infant pair observed, breastfeeding was timely initiated in 49.5% neonates. The timely initiation of breastfeeding was found to be higher among neonates who were placed skin-to-skin contact (34.9% vs 19.9%, p - value < 0.001). The timely initiation of breastfeeding was higher if the cord clamping was delayed than early cord clamped neonates (44.5% vs 35.3%, p - value < 0.001). In multivariate analysis, a mother with no obstetric complication during admission had 57% higher odds of timely initiation of breastfeeding (aOR 1.57; 95% CI 1.33, 1.86). Multiparity was associated with less timely initiation of breastfeeding (aOR 1.56; 95% CI 1.35, 1.82). Similarly, there was more common practice of timely initiation of breastfeeding among low birthweight neonates (aOR 1.46; 95% CI 1.21, 1.76). Neonates who were placed skin-to-skin contact with mother had more than two-fold higher odds of timely breastfeeding (aOR 2.52; 95% CI 2.19, 2.89). Likewise, neonates who had their cord intact for 3 min had 37% higher odds of timely breastfeeding (aOR 1.37; 95% CI 1.21, 1.55). The rate of timely initiation of breastfeeding practice is low in the health facilities of Nepal. Multiparity, no obstetric complication at admission, neonates placed in skin-to-skin contact and delay cord clamping were strong predictors for timely initiation of breastfeeding. Quality improvement intervention can improve skin-to-skin contact, delayed cord clamping and timely initiation of breastfeeding.


Lack of useful clinical predictors of response to splenectomy in patients with chronic idiopathic thrombocytopenic purpura.
We set out to identify clinical or analytical variables that might predict the response to splenectomy in patients with chronic idiopathic thrombocytopenic purpura (ITP). We retrospectively examined 138 mostly adult patients with chronic ITP, treated with splenectomy. Information was compiled from five Public Health Hospitals from a questionnaire and chart review. Sixty-one potentially prognostic variables were analysed by univariate and multivariate statistical methods. After multivariate analysis, age (relative risk = 1.02; CI 1-1.03) and a severity of the bleeding diathesis (relative risk = 1.6; CI 1.13-2.22) were independent prognostic factors for a sustained response to splenectomy. An independent analysis of the postsplenectomy counts showed that an early (days 1-3) thrombocyte count exceeding 156 x 10(9)/l cells increases the likelihood of a permanent unmaintained response. Our data indicate that the response to splenectomy in patients with chronic ITP cannot be adequately predicted on the basis of pre-splenectomy clinical or analytical variables.


Gold Nanoparticle-Labeled CRISPR-Cas13a Assay for the Sensitive Solid-State Nanopore Molecular Counting.
A gold nanoparticle (AuNP) labeled CRISPR-Cas13a nucleic acid assay has been developed for sensitive solid-state nanopore sensing. Instead of directly detecting the translocation of RNA through a nanopore, our system utilizes non-covalent conjugates of AuNPs and RNA targets. Upon CRISPR activation, the AuNPs are liberated from the RNA, isolated, and passed through a nanopore sensor. Detection of the AuNPs can be observed as increasing ionic current in the chip. Each AuNP that is detected is enumerated as an event, leading to quantitative of molecular targets. Leveraging the high signal-to-noise ratio enabled by the AuNPs, a detection limit of 50 fM before front-end target amplification is achieved using SARS-CoV-2 RNA segments as a Cas13 target. Furthermore, a dynamic range of six orders of magnitude is demonstrated for quantitative RNA sensing. This simplified AuNP-based CRISPR assay is performed at the physiological temperature without relying on thermal cyclers. In addition, the nanopore reader is similar in size to a smartphone, making the assay system suitable for rapid and portable nucleic acid biomarker detection in either low-resource settings or hospitals.


Supportive monitoring and disease management through the internet: an internet-delivered intervention strategy for recurrent depression.
Major depression is a highly prevalent, disabling disorder associated with loss of quality of life and large economic burden for the society. Depressive disorders often follow a chronic or recurrent course. The risk of relapses increases with each additional episode. The internet-deliverable intervention strategy SUMMIT (SUpportive Monitoring and Disease Management over the InTernet) for patients with recurrent depression has been developed with the main objectives to prolong symptom-free phases and to shorten symptom-loaden phases. This paper describes the study design of a six-sites, three-arm, randomized clinical trial intended to evaluate the efficacy of this novel strategy compared to treatment as usual (TAU). Two hundred thirty six patients who had been treated for their (at least) third depressive episode in one of the six participating psychiatric centers were randomized into one of three groups: 1) TAU plus a twelve-month SUMMIT program participation with personal support or 2) TAU plus a twelve-month SUMMIT program participation without personal support, or 3) TAU alone. Primary outcome of this study is defined as the number of "well weeks" over 24months after index treatment assessed by blind evaluators based on the Longitudinal Interval Follow-Up Evaluation. If efficacious, the low monetary and nonmonetary expenditures of this automated, yet individualized intervention may open new avenues for providing an acceptable, convenient, and affordable long-term disease management strategy to people with a chronic mental condition such as recurrent depression.


Localization of nitric oxide-synthesizing neurons sending projections to the dorsal raphe nucleus of the rat.
The origin of the nerve fibers immunoreactive for neuronal nitric oxide synthase (nNOS) in the rat dorsal raphe nucleus (DRN) was determined by combining the use of cholera toxin subunit b (CTb) as a retrograde tracer and nNOS immunohistochemistry with a monoclonal anti-nNOS antibody. Double labeled CTb-nNOS cell bodies were distributed from the rostral diencephalon to the caudal medulla oblongata, in about 20 areas of the brain. Several of the areas displaying double labeled cells are known for their involvement in the control of the sleep-wake cycle and/or transmission of nociception.


Efficiency, granulation, and bacterial populations related to pollutant removal in an upflow microaerobic sludge reactor treating wastewater with low COD/TN ratio.
In this study, a novel upflow microaerobic sludge reactor (UMSR) was constructed to conduct anaerobic digestion of municipal wastewater with low carbon and nitrogen ratio (C/N). Oxygen in the UMSR was supplied by falling water and external recirculation. Excellent nitrogen removal performance was obtained in the UMSR for treating wastewater with low C/N ratio at a temperature of 25 °C and a hydraulic retention time of 24 h. Ammonium and total nitrogen removal efficiencies averaged 92.35% and 90.41%, respectively, and sludge granulation occurred during acclimation. The inferred metabolism of nitrogen removal and ecological positions of functional microbe were integrated into a granule model by scanning electron microscopy. Additionally, the analysis of microbial community indicated that aerobic nitrifying bacteria and heterotrophic bacteria survived on the surface of sludge floc and granules while the anaerobic autotrophic, heterotrophic denitrifying, and anaerobic ammonia oxidation bacteria were present in the inner layer.


The contribution of self-efficacy and depression to disability and work status in chronic pain patients: a comparison between Australian and Brazilian samples.
There is evidence that cognitions (beliefs) and mood contribute to physical disability and work status in people with chronic pain. However, most of the current evidence comes from North America and Europe. This study examined the contribution of demographic, pain and psychosocial factors to disability and work status in chronic pain patients in two matched samples from quite different countries (Australia and Brazil). Data were collected from 311 chronic pain patients in each country. The results suggest that although demographic and pain variables (especially pain levels) contribute to disability, self-efficacy beliefs made a significant contribution to disability in both samples. Age and educational level also contributed to unemployment in both samples. But there were some differences, with self-efficacy and physical disability contributing to work status only in the Brazilian sample. In contrast, depression was the only psychological risk factor for unemployment in the Australian sample. Catastrophising and pain acceptance did not contribute to disability or unemployment in either sample. These findings confirm key aspects of biopsychosocial models of pain in two culturally and linguistically different chronic pain samples from different countries. They suggest that different chronic pain populations may share more similarities than differences.


Analyzing the hospice market.
Hospitals should base decisions about hospice services on need rather than on subjective feelings. Marketing methods can be used to identify the potential population for hospice care.


Peptides derived from repulsive guidance molecule act as antagonists.
Repulsive guidance molecule (RGM) is a membrane-bound protein that was originally identified as an axon guidance molecule in the visual system [T. Yamashita, B.K. Mueller, K. Hata, Neogenin and RGM signaling in the central nervous system, Curr. Opin. Neurobiol. 17 (2007) 29-34]. Functional studies in Xenopus and chick embryos have revealed the roles of RGM in axon guidance and laminar patterning, while those in mouse embryos have demonstrated its function in regulating the cephalic neural tube closure. Importantly, RGM inhibition enhanced the growth of injured axons and promoted functional recovery after spinal cord injury in rats. Here, we identified two RGMa-derived peptides that functioned as antagonists against RGMa. The peptides studied in vitro dose-dependently suppressed the neurite growth inhibition and growth cone collapse induced by RGMa. Thus, these peptides are promising reagents to treat injuries of the central nervous system.


Synthesis and in vitro cytotoxicity evaluation of star-shaped polymethacrylic conjugates with methotrexate or acitretin as potential antipsoriatic prodrugs.
Water-soluble polymer-drug conjugates were obtained and analyzed towards their potential use as prodrugs for two hydrophobic antipsoriatic agents, including methotrexate (MTX) and acitretin (AC). The conjugation efficacy of MTX decreased with a decreasing molar ratio of N,N-dimethylaminoethyl methacrylate (DMAEMA) repeating units in the polymethacrylic chains. Cytotoxicity of positively charged (from +5 to +10 mV) nano- and microparticles (3-1500 nm in DMEM at 37 °C) were estimated by in vitro MTT and Annexin-V apoptosis assays on Me45, NHDF, HaCaT and BEAS-2B cell lines. Further, cell cycle analysis revealed arrest in G0/G1 phase in melanoma cells, while neither apoptosis induction nor cell cycle arrest occurred in normal epidermal and epithelial cells. Tested conjugates displayed a novel cytostatic effect in Me45 cells and a pro-apoptotic effect in HaCaT cells. Epithelial BEAS-2B cells were the most sensitive to the tested conjugates and responded via induction of necrosis. Cell line models allowed for characterization of the biologically relevant potential action of pro-drugs. Additionally, a skin in vitro evaluation assay provided the first known evidence of side-effect reduction with pro-drug use. Histological examinations confirmed the lack of negative effects of conjugates on the skin and showed no irritating properties.


Coordinative Stabilization of Single Bismuth Sites in a Carbon-Nitrogen Matrix to Generate Atom-Efficient Catalysts for Electrochemical Nitrate Reduction to Ammonia.
Electrochemical nitrate reduction to ammonia powered by renewable electricity is not only a promising alternative to the established energy-intense and non-ecofriendly Haber-Bosch reaction for ammonia generation but also a future contributor to the ever-more important denitrification schemes. Nevertheless, this reaction is still impeded by the lack of understanding for the underlying reaction mechanism on the molecular scale which is necessary for the rational design of active, selective, and stable electrocatalysts. Herein, a novel single-site bismuth catalyst (Bi-N-C) for nitrate electroreduction is reported to produce ammonia with maximum Faradaic efficiency of 88.7% and at a high rate of 1.38 mg h-1 mgcat -1 at -0.35 V versus reversible hydrogen electrode (RHE). The active center (described as BiN2 C2 ) is uncovered by detailed structural analysis. Coupled density functional theory calculations are applied to analyze the reaction mechanism and potential rate-limiting steps for nitrate reduction based on the BiN2 C2 model. The findings highlight the importance of model catalysts to utilize the potential of nitrate reduction as a new-generation nitrogen-management technology based on the construction of efficient active sites.


Imperforate hymen with hematocolpos.
Presented are two cases of imperforate hymen with hematocolpos seen in a pediatric emergency department (ED) during a seven-month period. The first case presented with abdominal pain, urinary obstruction, and constipation on initial visit. The diagnosis was not made on the initial presentation. The patient was seen a second time, and final diagnosis was not made until a third visit to the pediatric outpatient clinic. The second case presented with syncope and bilateral lower abdominal pain. Ultrasound and subsequent surgery confirmed the physical findings in the ED of imperforate hymen and hematocolpos. Both patients underwent hymenectomy, and they have experienced no further symptoms.