S100PBP is regulated by mutated KRAS and plays a tumour suppressor role in pancreatic cancer.

We have previously shown that expression of S100PBP, an S100P binding partner, gradually decreases during progression of pancreatic ductal adenocarcinomas (PDAC). Here, we show that loss of S100PBP leads to oncogenic transformation of pancreatic cells; after deregulation of S100PBP expression, both in silico and in vitro analyses highlighted alterations of genes known to modulate cytoskeleton, cell motility and survival. Overexpression of S100P reduced S100PBP expression, while co-immunoprecipitation indicated the interaction of S100P with S100PBP-p53-ubiquitin protein complex, likely causing S100PBP degradation. The doxycycline-induced KrasG12D activation resulted in decreased S100PBP levels, while low-dose treatment with HDAC inhibitor MS-275 rescued its expression in both human and mouse PDAC cell lines. This indicates KrasG12D as an upstream epigenetic regulator of S100PBP. Finally, analysis of TCGA PanCancer Atlas PDAC datasets demonstrated poor prognosis in patients with high S100P and low S100PBP expression, suggesting that S100PBP is a novel tumour suppressor gene with potential clinical utility.

In situ spatiotemporal characterization and analysis of chemical reactions using an ATR-integrated microfluidic reactor.

Determining kinetic reaction parameters with great detail has been of utmost importance in the field of chemical reaction engineering. However, commonly used experimental and computational methods however are unable to provide sufficiently resolved spatiotemporal information that can aid in the process of understanding these chemical reactions. With our work, we demonstrate the use of a custom designed single-bounce ATR-integrated microfluidic reactor to obtain spatiotemporal resolution for in situ monitoring of chemical reactions. Having a single-bounce ATR accessory allows us to individually address different sensing areas, thereby providing the ability to obtain spatially and temporally resolved information. To further enhance the spatial resolution, we utilize the benefits of synchrotron IR radiation with the smallest beam spot-size ∼150 µm. An on-flow modular microreactor additionally allows us to monitor the chemical reaction in situ, where the temporal characterization can be controlled with the operational flowrate. With a unique combination of experimental measurements and numerical simulations, we characterize and analyse a model SN2 reaction. For a chemical reaction between benzyl bromide (BB) and sodium azide (SA) to produce benzyl azide (BA), we successfully show the capability of our device to determine the diffusion coefficients of BB and SA as 0.367 ± 0.115 10-9 m2 s-1 and 1.17 ± 0.723 10-9 m2 s-1, respectively. Finally, with the above characteristics of our device, we also calculate a reaction rate of k = 0.0005 (m3s-1mol-1) for the given chemical reaction.

Transfusion support for a woman with RHD*09.01.02 and the novel RHD*01W.161 allele in trans.

According to recent work group recommendations, individuals with the serologic weak D phenotypes should be RHD genotyped and individuals with molecular weak D types 1, 2, 3, 4.0, or 4.1 should be treated as D+. We report an African American woman with a long-standing history of metrorrhagia, who presented for infertility evaluation. Blood grouping showed AB with a possible subgroup of A, based on mixed-field agglutination, and a serologic weak D phenotype. Results from routine red cell genotyping for the RHD gene was incongruent with the serologic RhCE phenotype. For the surgical procedure, the patient was hence scheduled to receive group AB, D- RBC transfusions. Subsequent molecular analysis identified the ABO*A2.01 and ABO*B.01 alleles for the ABO genotype and the novel RHD allele [NG_007494.1(RHD):c.611T>A] along with an RHD*09.01.02 allele for the RHD genotype. Using a panel of monoclonal anti-D reagents, we showed the novel RHD(I204K) allele to represent a serologic weak D phenotype, despite occurring as a compound heterozygote, designated RHD*weak D type 161 (RHD*01W.161). Individuals with a weak D type 4.2 allele are prone to anti-D immunization, while the immunization potential of novel RHD alleles is difficult to predict. For now, patients should be treated as D- in transfusion and pregnancy management, when they harbor a novel RHD allele along with any weak D allele other than weak D types 1, 2, 3, 4.0, or 4.1. This study exemplifies strategies for how and when a laboratory should proceed from routine genotyping to nucleotide sequencing before any decisions on transfusion practice is made.

Enhanced biogas production potential analysis of rice straw: Biomass characterization, kinetics and anaerobic co-digestion investigations.

Present study of the biofuel potential of rice straw (RS) waste biomass materials. The average activation energy of rice straw was determined from KAS, FWO and Starink are 84.11, 89.62 and 84.52 kJ/mol, respectively. The characterized rice straw biomass has been tested for biogas potential under co-digestion mode of rice straw and cow dung in ratio 1/2. The maximum 339 ml/g Vs of biogas has been recorded in 35 days with CH4 concentration of 58.3%. The rest being CO2 as well as H2S has been found in trace amounts with observed 85% total solids and 74% volatile solids, present in rice straw.

Adult attention-deficit Hyperactivity disorder: From clinical reality toward conceptual clarity.

There is ambiguity about the clinical picture and concept of attention-deficit hyperactivity disorder (ADHD) in adults. Relevant literature was extracted from various search engines, analyzed, and interpreted. Available literature suggests a significant prevalence of ADHD in the adult population affecting the quality of socio-occupational functioning. Inattentiveness was more commonly present than hyperactivity-impulsivity. Frequent comorbidities with other psychiatric disorders like anxiety disorders and substance use disorders were noted. Pharmacological management and psychotherapy have been found effective in its management. ADHD is a disorder across the lifespan and fairly prevalent among adults. Greater awareness and more research are required for a better understanding of Adult ADHD and its effective management.

Transfusion support during childbirth for a woman with anti-U and the RHD*weak D type 4.0 allele.

D- red blood cells (RBCs), always in short supply, and Rh immune globulin (RhIG) are not needed for patient care if D+ RBCs can safely be transfused. According to a recent work group recommendation, patients with the RHD*weak D type 4.0 allele can be considered D+. We report an African American woman who presented for delivery at the end of the third trimester, at which time anti-U and a serologic weak D phenotype were recognized, requiring U-, D- RBC units. We obtained 3 U- RBC units, including 1 D- unit. Later, the RHD*weak D type 4.0 allele was determined by RHD genotyping, only 6 days before delivery. The patient had an uneventful vaginal delivery of a D+ baby. No transfusion was needed for mother or baby. In this case, a pregnant woman with the RHD*weak D type 4.0 allele can safely be managed as D+, relaxing the unnecessary D- restriction for the limited U- RBC supply. The procured U-, D- RBC unit was frozen with 14 days of shelf-life remaining. To conserve D- RBC units, not limited to U-, for patients with a definite need, we recommend molecular analysis of a serologic weak D phenotype before a transfusion becomes imminent. The best time to resolve a serologic weak D phenotype with RHD genotyping is early in a pregnancy. Immunohematology 2021;37:1-4 .D­ red blood cells (RBCs), always in short supply, and Rh immune globulin (RhIG) are not needed for patient care if D+ RBCs can safely be transfused. According to a recent work group recommendation, patients with the RHD*weak D type 4.0 allele can be considered D+. We report an African American woman who presented for delivery at the end of the third trimester, at which time anti-U and a serologic weak D phenotype were recognized, requiring U­, D­ RBC units. We obtained 3 U­ RBC units, including 1 D­ unit. Later, the RHD*weak D type 4.0 allele was determined by RHD genotyping, only 6 days before delivery. The patient had an uneventful vaginal delivery of a D+ baby. No transfusion was needed for mother or baby. In this case, a pregnant woman with the RHD*weak D type 4.0 allele can safely be managed as D+, relaxing the unnecessary D­ restriction for the limited U­ RBC supply. The procured U­, D­ RBC unit was frozen with 14 days of shelf-life remaining. To conserve D­ RBC units, not limited to U­, for patients with a definite need, we recommend molecular analysis of a serologic weak D phenotype before a transfusion becomes imminent. The best time to resolve a serologic weak D phenotype with RHD genotyping is early in a pregnancy. Immunohematology 2021;37:1­4 .

Short-course radiotherapy with consolidation chemotherapy versus conventionally fractionated long-course chemoradiotherapy for locally advanced rectal cancer: randomized clinical trial.

BACKGROUND: The trial hypothesis was that, in a resource-constrained situation, short-course radiotherapy would improve treatment compliance compared with conventional chemoradiotherapy for locally advanced rectal cancer, without compromising oncological outcomes. METHODS: In this open-label RCT, patients with cT3, cT4 or node-positive non-metastatic rectal cancer were allocated randomly to 5 × 5 Gy radiotherapy and two cycles of XELOX (arm A) or chemoradiotherapy with concurrent capecitabine (arm B), followed by total mesorectal excision in both arms. All patients received a further six cycles of adjuvant chemotherapy with the XELOX regimen. The primary endpoint was treatment compliance, defined as the ability to complete planned treatment, including neoadjuvant radiochemotherapy, surgery, and adjuvant chemotherapy to a dose of six cycles. RESULTS: Of 162 allocated patients, 140 were eligible for analysis: 69 in arm A and 71 in arm B. Compliance with planned treatment (primary endpoint) was greater in arm A (63 versus 41 per cent; P = 0.005). The incidence of acute toxicities of neoadjuvant therapy was similar (haematological: 28 versus 32 per cent, P = 0.533; gastrointestinal: 14 versus 21 per cent, P = 0.305; grade III-IV: 2 versus 4 per cent, P = 1.000). Delays in radiotherapy were less common in arm A (9 versus 45 per cent; P < 0.001), and overall times for completion of neoadjuvant treatment were shorter (P < 0.001). The rates of R0 resection (87 versus 90 per cent; P = 0.554), sphincter preservation (32 versus 35 per cent; P = 0.708), pathological complete response (12 versus 10 per cent; P = 0.740), and overall tumour downstaging (75 versus 75 per cent; P = 0.920) were similar. Downstaging of the primary tumour (ypT) was more common in arm A (P = 0.044). There was no difference in postoperative complications between trial arms (P = 0.838). CONCLUSION: Reduced treatment delays and a higher rate of compliance were observed with treatment for short-course radiotherapy with consolidation chemotherapy, with no difference in early oncological surgical outcomes. In time- and resource-constrained rectal cancer units in developing countries, short-course radiotherapy should be the standard of care.

First-episode psychosis: How long does it last? A review of evolution and trajectory.

Study of first-episode psychosis (FEP), an episode of psychotic nature which manifests for the first time in an individual in the longitudinal continuum of his/her illness, has been study matter of research interest in recent years. A comprehensive review of the literature will help us understand the evolution and trajectory of this concept better. A literature review of available articles addressing the concept, phenomenology, evolution, identification, course, and outcome of FEP was done; the same was subsequently divided into broad topics for better clarity and analyzed. FEP constituted a clinical psychotic phenomenon with underlying significant heterogeneity in diagnosis, stability, course, and outcome. The study has attempted to view FEP both as horizontal spectrum across various diagnoses and longitudinally ranging from asymptomatic individual with unknown risk status to attenuated psychosis to multiple relapses/unremitting illness. Many risk and protective factors have been brought out with varying certainty ranging bio-psycho-social spectrum. Efforts have been made to calculate polygenic risk score based on genes involvement/sharing between various psychotic spectrum disorders; as well as biomarker panels to identify people at risk. FEP may prove to be an important concept to understand psychosis in general; without putting things into the diagnostic rubric. It may help understand multiple risk and protective factors for the course and outcome of psychotic illness and may clear the cloud to sharpen the evidence toward commonality and distinctiveness between various psychotic diagnoses in vogue for more comprehensive concept.

Repulsion leads to coupled dislocation motion and extended work hardening in bcc metals.

Work hardening in bcc single crystals at low homologous temperature shows a strong orientation-dependent hardening for high symmetry loading, which is not captured by classical dislocation density based models. We demonstrate here that the high activation barrier for screw dislocation glide motion in tungsten results in repulsive interactions between screw dislocations, and triggers dislocation motion at applied loading conditions where it is not expected. In situ transmission electron microscopy and atomistically informed discrete dislocation dynamics simulations confirm coupled dislocation motion and vanishing obstacle strength for repulsive screw dislocations, compatible with the kink pair mechanism of dislocation motion in the thermally activated (low temperature) regime. We implement this additional contribution to plastic strain in a modified crystal plasticity framework and show that it can explain the extended work hardening regime observed for [100] oriented tungsten single crystal. This may contribute to better understanding the increase in ductility of highly deformed bcc metals.

Role of various lifestyle and behavioral strategies in positive mental health across a preventive to therapeutic continuum.

There is growing interest in lifestyle and behavioral strategies not only in prevention but also in the management of psychiatric morbidity. Available literature in this direction was accessed, and the role of various lifestyle and behavioral factors was explored. There is strong evidence of the role of good sleep, nutritious diet, exercise, social connectedness, enhanced self-esteem, sense of purpose in life, resilience, mindfulness, and environmental mastery in the promotion of mental well-being and prevention and management of psychiatric disorders. There is a significant scope of lifestyle and behavioral intervention in ensuring positive mental health spanning from preventive to therapeutic dimension.

Workplace based assessment: A review of available tools and their relevance.

Workplace-based assessment (WPBA) appears to be a promising tool for more comprehensive assessment of the learners. Relevant literature in this direction was collated and analyzed for its relevance, salience, and merit. Many WPBA tools are being used by various educational institutions which spans across multiple domains and over the entire duration of the workplace learning. It caters to holistic assessment with structured measures, real-time feedback, and continuous professional development. It is being used more for formative assessment and has limited utility in summative assessment as on date. WPBA tools have promising prospect in bringing novelty, objectivity, and holistic approach in assessment.

Genetic polymorphisms in DNA repair genes and their association with cervical cancer.

Background and objective: Carcinoma of cervix is the second most common cancer among women worldwide. The DNA repair network plays an important role in the maintenance of genetic stability, protection against DNA damage and carcinogenesis. Alterations in repair genes XRCC1, XRCC2 and XRCC3 and been reported in certain cancers. We hypothesised an association between XRCC1+399A/G, XRCC2+31467G/A and XRCC3+18067C/T polymorphisms and the risk of cervical cancer. Subjects and methods: This study included 525 subjects (265 controls and 260 cervical cancer cases). Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: Women with GA and AA genotypes of XRCC1+399A/G showed 2.4-3.8 fold higher risk of cervical cancer (P = 0.001). The +399A* allele was significantly linked with cervical cancer (P = 0.002). However, XRCC2+31479G/A and XRCC3+18067C/T polymorphisms did not show any statistically significant associations. Conclusion: The XRCC1+399A/G SNP is linked with cervical cancer. We suggest that this variant can be utilized as a prognostic marker for determination of cervical cancer susceptibility.

Evaluation of Volumetric Doses of Organs at Risk in Carcinoma Cervix Patients with HDR Intracavitary Brachytherapy and Comparison of CT-based and Conventional Plans.

BACKGROUND: Brachytherapy treatment planning in cervix carcinoma patients using two dimensional (2D) orthogonal images provides only point dose estimates while CT-based planning provides volumetric dose assessment helping in understanding the correlation between morbidity and the dose to organs at risk (OARs) and treatment volume. OBJECTIVE: Aim of present study is to compare International Commission on Radiation Units and Measurements Report 38 (ICRU 38) reference point doses to OARs with volumetric doses using 2D images and CT images in patients with cervical cancer. MATERIAL AND METHODS: In this prospective study, 20 patients with cervical cancer stages (IIB-IIIB) were planned for a brachytherapy dose of 7Gy per fraction for three fractions using 2D image-based treatment plan and CT-based plan. ICRU 38 points for bladder and rectum were identified on both 2D image-based plan and CT-based plan and doses (DICRU) at these points were compared to the minimum dose to 2cc volume (D2cc) of bladder and rectum receiving the highest dose. RESULTS: D2cc bladder dose was 1.60 (±0.67) times more than DICRUb bladder dose whereas D2cc rectum dose was 1.13±0.40 times DICRUr. Significant difference was found between DICRUb and D2cc dose for bladder (p=.0.016) while no significant difference was seen between DICRUr and D2cc dose for rectum (p=0.964). CONCLUSION: The study suggests that ICRU 38 point doses are not the true representation of maximum doses to OARs. CT-based treatment planning is more a reliable tool for OAR dose assessment than the conventional 2D radiograph-based plan.

An unusual case of intestinal obstruction due to internal herniation from adhesions between two appendices epiploicae.

Internal hernia of the small bowel is a rare finding especially in previously non-operated abdomen. Such a hernia occurring due to involvement of appendices epiploicae is an even rare instance with less than five reported cases in the literature. We encountered a 75-year-old male who had internal herniation of small bowel through an aperture created by adhesion between two appendices epiploicae in a previously virgin abdomen. Laparotomy and division of adhesion was performed to manage him successfully. Even in a virgin abdomen, a high index of suspicion along with early intervention is the key to reduction in mortality and morbidity in cases intestinal obstruction.

Complete on/off responsive ParaCEST MRI contrast agents for copper and zinc.

Two thulium-based ParaCEST responsive contrast agents, Tm-DOTAm-py and Tm-DOTAm-ßAla-py, have been synthesized and evaluated for imaging copper and zinc. Unusual for responsive MRI contrast agents, both agents display a complete on/off response in the presence of transition metals. Both complexes function as paraCEST agents in the absence of copper and zinc, with the positively charged Tm-DOTAm-py being more sensitive than the neutrally charged Tm-DOTAm-ßAla-py. In each case, the CEST signal arises from amide protons rather than from a water molecule coordinated to Tm3+ ions. Upon binding to Cu+, Cu2+, or Zn2+, the exchange rate of the amide protons increases substantially, resulting in a complete loss of the CEST signal. This efficient mode of action along with the lack of inner-sphere water molecules both in the presence and absence of transition metals was confirmed by 1/T1 NMRD profiles, 17O NMR measurements, and molecular modelling simulations. Neither complex is selective for copper over zinc. Both form either a 1 : 1 TmL : Cu+ or a 2 : 1 TmL : Cu2+ and TmL : Zn2+ complexes with binding affinities comparable to that of other responsive MRI contrast agents and sensitivity comparable to that of other CEST contrast agents.

Impact of GSTM1, GSTT1 and GSTP1 genes polymorphisms on clinical toxicities and response to concomitant chemoradiotherapy in cervical cancer.

BACKGROUND: Certain forms of chemoradiotherapy generate toxic reactive oxygen species, which may be ameliorated by antioxidant enzymes such as glutathione S-transferase (GST). Genetic polymorphisms of GST may predict treatment outcomes and can be used as genetic marker to screen patients before treatment. We hypothesised an effect of GST polymorphisms on the response and toxicities produced by chemoradiation therapy. MATERIALS AND METHODS: GST polymorphisms were determined by multiplex polymerase chain reaction and PCR-restriction fragment length polymorphism (PCR-RFLP) in 227 women with cervical cancer receiving cisplatin based chemoradiotherapy. Treatment response and toxicities were evaluated by standard internationally recognised criteria (RECIST and RTOG). RESULTS: Severe (grade 3-4) gastrointestinal and haematological toxicities were present in 22 (9.4%) and 16 (7.0%) patients, respectively. GSTM1 null, GSTT1 null and GSTP1 AG genotypes brought marginally better non-significant associations. In single locus analysis GSTP1 AG and GG was linked to greatest risk of severe (grade 3-4) gastrointestinal toxicity (OR = 3.12, P = 0.035 and OR = 6.99, P = 0.01, respectively). In gene-gene interaction analysis, GSTM1 null-GSTP1 GG showed 4.2-fold higher risk of severe gastrointestinal toxicity (P = 0.014). GSTT1 null-GSTP1 AG reached statistical significance with a 3.9-fold higher risk of high grade gastrointestinal toxicity (P = 0.038). CONCLUSIONS: Although no significant links were found between GST polymorphism and treatment response, null genotypes of GSTM1, GSTT1 and 'G' allele of GSTP1 bring a higher risk of severe gastrointestinal toxicity due to chemoradiation therapy in cervical cancer.

Achieving selectivity for copper over zinc with luminescent terbium probes bearing phenanthridine antennas.

A family of terbium probes was synthesized and evaluated for the luminescence detection of copper and zinc in water at neutral pH. Each probe incorporates a terbium ion chelated by a macrocyclic polyaminocarboxylate and conjugated to either one, two, or three phenanthridine antennas via a diamine linker. All three probes, Tb-1Phen, Tb-2Phen, and Tb-3Phen, exhibit similar responses toward copper and zinc. In each case, the terbium-centered time-gated phosphorescence decreases upon binding either CuI or CuII but not upon addition of ZnII. The phosphorescence of Tb-2Phen is also not significantly affected by other metal ions including MgII, CaII, MnII, FeII, NiII, CdII, and HgII. Tb-1Phen, on the other hand, responds weakly to MnII, FeII and NiII. The lack of affinity of each probe for ZnII was further confirmed by competition experiments with CuI and CuII. Notably, whereas the terbium-centered emission of each probe is quenched upon copper coordination, the phenanthridine-centered luminescence emission is not. As such, each probe functions as a ratiometric probe for the selective detection of copper over zinc. Theoretical calculations further demonstrate that the turn off response of the probe is due to an increase in the distance separating the lanthanide ion from its phenanthridine antennas upon coordination of copper, which in turn decreases the efficiency of terbium sensitization by the phenanthridines.