Progressive plasticity during colorectal cancer metastasis.

As cancers progress, they become increasingly aggressive-metastatic tumours are less responsive to first-line therapies than primary tumours, they acquire resistance to successive therapies and eventually cause death1,2. Mutations are largely conserved between primary and metastatic tumours from the same patients, suggesting that non-genetic phenotypic plasticity has a major role in cancer progression and therapy resistance3-5. However, we lack an understanding of metastatic cell states and the mechanisms by which they transition. Here, in a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that, although primary tumours largely adopt LGR5+ intestinal stem-like states, metastases display progressive plasticity. Cancer cells lose intestinal cell identities and reprogram into a highly conserved fetal progenitor state before undergoing non-canonical differentiation into divergent squamous and neuroendocrine-like states, a process that is exacerbated in metastasis and by chemotherapy and is associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues compared with their intestinal lineage-restricted primary tumour counterparts. We identify PROX1 as a repressor of non-intestinal lineage in the fetal progenitor state, and show that downregulation of PROX1 licenses non-canonical reprogramming.

Subtle membrane changes in cryopreserved bull spermatozoa when modified temperature drop rates are used during the first phase of freezing.

BACKGROUND: Cryopreservation of spermatozoa involves reduction of temperature to a subzero level, leading to increased longevity. However, temperature reduction has a significant effect on sperm membranes. OBJECTIVE: To evaluate the impact of the rate of temperature drop during the first phase of freezing on subtle membrane changes in cryopreserved bull spermatozoa. MATERIALS AND METHODS: Thirty-two ejaculates from four bulls (eight ejaculates/bull) were collected using artificial vagina while keeping a 3 to 4 days gap between two collections. Diluted semen samples were equilibrated at 5 degree C for 4 hours. The samples were then placed in a pre-programmed semen freezer. The first phase of freezing, that is, 5 degree C till -10 degree C was subjected to three different temperature drop rates: accelerated (F1), moderate (F2), and slow (F3), at 20 degree C per min, 10 degree C per min and 5 degree C per min, respectively. After thawing, spermatozoa were assessed for percentage live, plasma, and acrosomal membrane integrity, along with the external appearance of phosphatidyl serine, indicating apoptosis. RESULTS: A significant difference (p < 0.05) in viability, plasma membrane integrity (HOS test), and acrosome membrane integrity (PSA test) was observed between F3 and the other groups. However, the parameters did not significantly differ between F1 and F2. The annexin V-PI assay (AN/PI) categorized four types of sperm populations: non-apoptotic and viable (AN-/PI-), apoptotic and viable (AN+/PI-), non-apoptotic and non-viable (AN-/PI+), and apoptotic and non-viable (AN+/PI+). The proportion of spermatozoa with (AN-/PI-) and (AN+/PI+) differed significantly (p < 0.05) between F3 and the other groups. The values for apoptotic and viable (AN+/PI-) and non-apoptotic and non-viable (AN-/PI+) sperm were not significantly different among all freezing categories. CONCLUSION: A slower temperature drop rate (freezing rate) during the first phase of freezing results in less damaging, subtle membrane changes. Doi.org/10.54680/fr24410110312.

Vallaris solanacea induces mitochondrial mediated apoptosis in HL-60 human promyelocytic leukemia cells.

In the present study, the apoptosis-inducing potential of a chloroform fraction from an alcoholic extract of Vallaris solanacea aerial parts (VS) was examined using human promyelocytic leukemia HL-60 cells. We discovered a concentration and time-dependent decrease in cell growth using MTT assay. Scanning electron micrographs and fluorescence microscopy were used to observe several well-documented morphological and nuclear alterations, such as reduction in cell size, chromatin condensation, fragmentation, and the creation of cell surface blebs. A considerable rise in the Sub-G0 population was revealed by cell cycle analysis. Additionally, a dose-dependent rise in cells positive for Annexin V was observed. DCFH-DA test on VS-treated HL-60 cells showed an increase in endogenous ROS generation of up to 4.3 fold. Additionally, suppression in Bcl-2 levels and increased mitochondrial membrane depolarization in treated cells were also associated with a rise in cytosolic cytochrome-c levels that was consequently followed by the activation of the caspase cascade. Further, the DNA fragmentation assay exhibited a typical ladder formation at 25 µg/ml, which became prominent in a concentration-dependent manner. Our study revealed that VS has apoptosis-inducing potential towards HL-60 cells in vitro and is an effective candidate for further anti-cancer studies.

Treatment of hypoplastic left heart syndrome: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: This meta-analysis aimed to consolidate existing data from randomised controlled trials on hypoplastic left heart syndrome. METHODS: Hypoplastic left heart syndrome specific randomised controlled trials published between January 2005 and September 2021 in MEDLINE, EMBASE, and Cochrane databases were included. Regardless of clinical outcomes, we included all randomised controlled trials about hypoplastic left heart syndrome and categorised them according to their results. Two reviewers independently assessed for eligibility, relevance, and data extraction. The primary outcome was mortality after Norwood surgery. Study quality and heterogeneity were assessed. A random-effects model was used for analysis. RESULTS: Of the 33 included randomised controlled trials, 21 compared right ventricle-to-pulmonary artery shunt and modified Blalock-Taussig-Thomas shunt during the Norwood procedure, and 12 regarded medication, surgical strategy, cardiopulmonary bypass tactics, and ICU management. Survival rates up to 1 year were superior in the right ventricle-to-pulmonary artery shunt group; this difference began to disappear at 3 years and remained unchanged until 6 years. The right ventricle-to-pulmonary artery shunt group had a significantly higher reintervention rate from the interstage to the 6-year follow-up period. Right ventricular function was better in the modified Blalock-Taussig-Thomas shunt group 1-3 years after the Norwood procedure, but its superiority diminished in the 6-year follow-up. Randomised controlled trials regarding medical treatment, surgical strategy during cardiopulmonary bypass, and ICU management yielded insignificant results. CONCLUSIONS: Although right ventricle-to-pulmonary artery shunt appeared to be superior in the early period, the two shunts applied during the Norwood procedure demonstrated comparable long-term prognosis despite high reintervention rates in right ventricle-to-pulmonary artery shunt due to pulmonary artery stenosis. For medical/perioperative management of hypoplastic left heart syndrome, further randomised controlled trials are needed to deliver specific evidence-based recommendations.

Progressive plasticity during colorectal cancer metastasis.

Metastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt LGR5 + intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cancer cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues than their intestinal lineage-restricted primary tumor counterparts. We identify PROX1 as a stabilizer of intestinal lineage in the fetal progenitor state, whose downregulation licenses non-canonical reprogramming.

Effects of Ultrasound-Guided Lower Extremity Nerve Blocks for Below-Knee Procedures in the Emergency Department of a Tertiary Care Hospital, Central Gujarat.

Background and objectives Ultrasound-guided femoral and popliteal sciatic nerve blocks are useful adjuncts for many below-knee procedures like debridement, amputation, etc. The objectives of the study were to find the efficacy and feasibility of the ultrasound-guided combined femoral and popliteal sciatic nerve block for below-knee procedures in the Emergency Medicine Department (ED). Methodology This prospective clinical study was carried out over three months in ED. A total of 30 patients undergoing below-knee procedures were included in the study. Femoral and popliteal sciatic nerve blocks were administered to each patient using the high-frequency linear ultrasound probe by emergency physicians trained in ultrasound. The effect of blocks, amount of local anesthetic (LA) used, duration of the procedure, and post-block analgesia were recorded. Patients were monitored for possible complications, if any. Data were entered and analyzed using a Microsoft Excel worksheet. Results The average volume of LAs required was around 34.5 cc for both blocks combined. No complications like vascular puncture or nerve injury were reported during the study. The time taken to complete the procedure was around 33 minutes, and the average time to achieve sensory block was around 9 minutes after completing the procedure. Conclusions An ultrasound-guided combined femoral and popliteal sciatic nerve block is an effective and feasible procedure and thus should be considered in ED for below-knee procedures.

Molecular docking-based interaction studies on imidazo[1,2-a] pyridine ethers and squaramides as anti-tubercular agents.

Development of new anti-tubercular agents is required in the wake of resistance to the existing and newly approved drugs through novel-validated targets like ATP synthase, etc. The major limitation of poor correlation between docking scores and biological activity by SBDD was overcome by a novel approach of quantitatively correlating the interactions of different amino acid residues present in the target protein structure with the activity. This approach well predicted the ATP synthase inhibitory activity of imidazo[1,2-a] pyridine ethers and squaramides (r = 0.84) in terms of Glu65b interactions. Hence, the models were developed on combined (r = 0.78), and training (r = 0.82) sets of 52, and 27 molecules, respectively. The training set model well predicted the diverse dataset (r = 0.84), test set (r = 0.755), and, external dataset (rext = 0.76). This model predicted three compounds from a focused library generated by incorporating the essential features of the ATP synthase inhibition with the pIC50 values in the range of 0.0508-0.1494 µM. Molecular dynamics simulation studies ascertain the stability of the protein structure and the docked poses of the ligands. The developed model(s) may be useful in the identification and optimization of novel compounds against TB.

38. Effect of Chlorhexidine Rinsed Blood Contamination on Bond Strength of Brackets Bonded with Self-etch Primer- An in Vitro Study.

The present invitro type of study has done to check the effect of blood contamination & chlorhexidine combination on the bond strength of brackets bonded with self-etch primer technique. The study consisted of ninety sound human upper premolars (extracted for orthodontic purpose) fixed in a self-cure acrylic block and segregated into three groups of 30 samples each. 0.022 slot metal MBT brackets (Gemini series-3M unitek) were bonded with self-etch primer using Transbond XT composite, CA, USA and light cure for 40 seconds) on clean buccal surface. Teeth were divided into 3 groups-Group A/Control group, Group B, Group C. A computer was used to record the force applied to debond the bonded bracket in the unit of Newton. The analysis of variance indicated that there were significant differences (F value = 6.891, p value=0.002) in bond strengths between the various groups tested. The highest value of shear bond strength occurred when chlorhexidine (Group C) was used to remove the blood contamination (mean=15.874 MPa). When bonding was done in ideal condition (Group A), shear bond strength obtained was slightly lower (mean=14.497 MPa) as compared to Group C. On the other hand, lowest shear bond strength among all three groups occurred when blood contamination (Group B) was removed with water (mean=11.059 MPa). Analysis of the study showed that shear bond strength of orthodontic brackets to enamel significantly decreased during bonding with self-etch primer in blood contamination condition. Self-etch primer displayed considerably superior performance with the use of chlorhexidine instead of water to wash the blood contamination.

Neutronic simulation of medical radioisotope 99Mo and 177Lu production in IPR 14 MeV neutron generator facility.

An accelerator based 14 MeV neutron generator is commissioned at Institute for Plasma Research India. The generator is based on the linear accelerator concept where the deuterium ion beam impinged to the tritium target to produce neutrons. The generator is designed to produce 1 × 1012 neutrons per sec. The 14 MeV neutron source facilities are an emerging tool for the lab scale experiments and research. In order to utilize the generator for the welfare of humanity, the assessment is made for the production of medical radioisotopes using the neutron facility. The usage of radioisotopes in the treatment and diagnosis of a disease is an important factor in the healthcare sector. A series of calculations are conducted to generate radioisotopes, especially 99Mo and 177Lu those are having huge applications in the medical and pharmaceutical industries. 99Mo can be also generated through neutron reactions 98Mo(n, g)99Mo and 100Mo(n, 2n)99Mo apart from fission reaction. The cross section of 98Mo(n, g)99Mo is high in the thermal energy range whereas 100Mo(n,2n)99Mo occurs at a high energy range. 177Lu can be produced using the reactions 176Lu (n, g)177Lu and 176Yb (n, g)177Yb. The cross section of both 177Lu production routes is higher at thermal energy range. The neutron flux level near the target is around 1010 cm-2s-1. In order to enhance production capabilities, the neutron energy spectrum moderators are used to thermalize the neutrons. The materials used as a moderator are beryllium, HDPE, graphite, etc. Moderators enhance the capabilities of medical isotope production in neutron generators.

Differential expression of inflammatory cytokines, prostaglandin synthases and secretory leukocyte protease inhibitor in the endometrium and circulation in different graded CEH-pyometra in bitch.

Cystic endometrial hyperplasia (CEH)-pyometra (CEH-P) is one of the most common reproductive disorders in bitches, posing a risk to both future fertility and life. The aims of the current study were to elucidate the differential expression patterns of inflammatory mediators at transcript and protein levels in the endometrium and to assess the concentrations of key inflammatory mediators in the peripheral circulation of bitches with different graded CEH-P. A total of 25 client-owned intact mixed breed bitches of 3-10 years presented to the outpatient department of RVP-TVCC of the institute were considered for the study. Of which, 22 cases suggestive of pyometra and 3 cases of CEH obtained during routine elective ovariohysterectomy were subjected to histopathological examination. Uteri were categorized into CEH (n = 3), moderate CEH-P (mCEH-P, n = 9), severe CEH-P (sCEH-P, n = 6) and atrophic pyometra (AT-P, n = 7). A group of age matched (n = 12) bitches without pyometra served as control. Endometrial transcripts such as IL6, IL8, PTGS2, PGFS, and SLPI were expressed differentially in the CEH and CEH-P bitch. In addition, a strong immunoreactivity (IR) of IL6, IL8, PTGS2, and mPGES1 was recorded in the sCEH-P uterus, while expression of IL10 was noticed in AT-P. In circulation, serum IL6 was the most relevant marker with high sensitivity of 96.2% and specificity of 84.6% at a cut off concentration 8.5 pg/mL followed by SLPI with 95.2% sensitivity, and 84.6% specificity at cut off concentration of 1.3 ng/mL. Serum IL10, PGFM and SLPI concentration in the peripheral circulation were 1.5-2.23 fold higher in mCEH-P, 0.87-2.5 fold higher in sCEH-P and 2.9-3.5 fold higher in AT-P than that of control. It is concluded that monitoring the serum concentration of IL6, IL10 and SLPI would be useful adjunct to the established hematobiochemical parameters in the management of pyometra in the bitch with critical illness.

A Study of Autologous Non-Cultured Epidermal Suspension (NCES) Transplant in Patients with Stable Vitiligo without the Use of NB-UVB.

Introduction:Vitiligo is a common form of localized depigmentation and an important public health problem which affects around one percent of the global population and about two percent of the population in India. The present study aimed to document the results and side effects of non-cultured melanocyte transplant in patients with stable vitiligo without post-procedure use of NB UVB. Methods:The present study was a prospective interventional study conducted among patients with stable vitiligo who were attending the outpatient department (OPD) of dermatology of a tertiary center of Delhi. Patients with stable vitiligo aged >10 years who gave their consent for non-cultured epidermal suspension (NCES) were included in the study. Autologous skin graft of size 0.2 mm was taken from the donor site and a melanocyte cell suspension was prepared using standardized procedure, which was later transplanted to the recipient area. All patients were asked to come for follow-up at the OPD after seven days, 15 days, one month, followed by every month till six months post-transplantation, and repigmentation was assessed visually by both graph paper and photography. Data was analyzed using SPSS vs. 21. Results:In our study, the majority of patients had vitiligo vulgaris (27 subjects with 47 patches). A total number of 59 patches were transplanted, of which 38 (64.4%) achieved excellent repigmentation, 28.8% good repigmentation, 3.4% fair repigmentation and 3.39% poor repigmentation. A total of 1302.5 cm² of the depigmented area was operated by NCES and the repigmentation of 874.5 cm2 (67.14%) was achieved by six months. Conclusion:The present study found that the majority of patients (93%) with vitiligo achieved excellent or good repigmentation after NCES and the rate of complication was very low.

Integration of Consolidation Chemotherapy After Concurrent Chemoradiation in the Treatment of Locally Advanced Uterine Cervical Cancer.

Background: Despite the current standard of concurrent chemoradiation (CCRT), around 30-40% are still dying from locally advanced cervical cancer. Increasing the radiation dose further was not a feasible option, but addition of chemotherapy further was tried due to the different toxicity profiles of it. So, the use of consolidation chemotherapy beyond CCRT has been studied. Aim: To evaluate the efficacy, toxicity, tumour response and loco-regional control following consolidation chemotherapy after concurrent chemoradiation in locally advanced carcinoma cervix (LACC). Methods: The patients were randomized into two arms: the conventional arm (control arm, n = 30) patients received conventional treatment with weekly injection cisplatin (35 mg/m2) concurrently with pelvic external beam radiation (50 Gy/25 fraction, 2 Gy/fraction, 5 fraction weekly) followed by intracavitary radiotherapy of 21 Gy in 3 fractions of 7 Gy each by HDR brachytherapy. In the interventional arm (study arm, n = 30), patients received the standard treatment followed by 3 cycles of consolidation chemotherapy (paclitaxel + carboplatin) every three weekly. Results: Haematological toxicity (grade 3 anaemia and grade 1 leucopenia, grade 1 and 2 thrombocytopenia) was higher in the study group. Renal, hepatic and gastrointestinal toxicity was more in the study arm. Peripheral neuropathy was mostly seen in the study arm. Median follow-up was 9 months. Treatment response was better, and the rate of recurrence was less in the study arm. Conclusion: Addition of few cycles of consolidation chemotherapy after standard treatment is beneficial in patients with LACC with manageable toxicity and good compliance.

MPS VII - Extending the classical phenotype.

Mucopolysaccharidosis VII (or Sly syndrome) is an autosomal recessive disorder characterised by a deficiency in the enzyme Beta-glucuronidase (GUSB). Partial degradation of glycosaminoglycans (GAGs); chondroitin sulfate (CS), dermatan sulfate (DS) and heparan sulfate (HS) results in the accumulation of these fragments in the lysosomes of many tissues, eventually leading to multisystem damage. In some cases, early diagnosis on clinical grounds alone can be difficult due to the extreme variability of the clinical presentation and disease progression. We present a case report of a 31-year-old male patient diagnosed with MPS VII at the age of 28, who multiple specialists saw without suspecting the diagnosis due to the unusual presentation. The patient presented with a history of developmental delay, scoliosis, kyphosis, corneal clouding, abnormal gait, short stature, hearing impairment, slightly coarse facial features and progressive deterioration of fine motor skills since childhood. The patient had inguinal hernia repair at around 12 months, bilateral hearing impairment with a left bone-anchored hearing aid, and spinal surgery. During spinal surveillance MPS VII was suspected by a spinal surgeon with interest in MPS, and the diagnosis confirmed with a deficiency in beta-glucuronidase in leucocytes and marginally elevated urinary GAGs. Next-generation sequencing identified two mutations in the GUSB gene (OMIM 611499), c.526C > T p.(Leu176Phe) and c.1820G > C p.(Gly607Ala). Although the patient exhibited features of the severe form of non-classical manifestations, his metabolic condition has remained reasonably stable, surviving into adulthood with only symptomatic treatment. We present the ever-expanding phenotypic spectrum of this ultra-rare disease.

Architectural analysis of root system and phytohormone biosynthetic genes expression in wheat (Triticum aestivum L.) inoculated with Penicillium oxalicum.

In this study, a fungal plant growth promoter Penicillium oxalicum T4 isolated from non-rhizosphere soil of Arunachal Pradesh, India, was screened for different plant growth promoting traits in a gnotobiotic study. Though inoculation improved the overall growth of the plants, critical differences were observed in root architecture. Confocal Laser Scanning Microscope, Scanning electron microscope and the stereo microscopic study showed that inoculated wheat plants could develop profuse root hairs as compared to control. Root scanning indicated improvement in cumulative root length, root area, root volume, number of forks, links, crossings, and other parameters. A confocal scanning laser microscope indicated signs of endophytic colonization in wheat roots. Gene expression studies revealed that inoculation of T4 modulated the genes affecting root hair development. Significant differences were marked in the expression levels of TaRSL4, TaEXPB1, TaEXPB23, PIN-FORMED protein, kaurene oxidase, lipoxygenase, ACC synthase, ACC oxidase, 9-cis-epoxycarotenoid dioxygenase, and ABA 8'-hydroxylase genes. These genes contribute to early plant development and ultimately to biomass accumulation and yield. The results suggested that P. oxalicum T4 has potential for growth promotion in wheat and perhaps also in other cereals.

The effectiveness of high-flow nasal cannula and standard non-rebreathing mask for oxygen therapy in moderate category COVID-19 pneumonia: Randomised controlled trial.

Background: COVID-19 caused by the highly infectious severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection is a matter of concern and has led to severe health problems all over the world. Oxygen therapy is the mainstay for the management of patients suffering from various stages of the disease. Objectives: To compare the effectiveness of high-flow nasal cannula (HFNC) and standard non-rebreathing mask (NRBM) as oxygen delivery devices in moderate cases of COVID-19 pneumonia. Methods: A single-centre, open-label, randomised controlled trial was conducted between February 2021 and April 2021. All the enrolled patients (N=120) were randomly allocated into two groups according to the oxygen delivery device used. Group 1 (n=60) received HFNC and group 2 (n=60) received NRBM as the initial oxygen delivery device, to maintain a target saturation ≥96% in both groups. The progression-free survival without escalation of respiratory support, partial pressure of arterial oxygen (PaO2 ), a ratio of partial pressure of arterial oxygen to fractional inspiratory oxygen concentration (PaO2 /FiO2 ), respiratory rate, heart rate, blood pressure, number of patients requiring non-invasive ventilation or endotracheal intubation, time for de-escalation of oxygen therapy to lower FiO2 device, time to progression to severe disease, survival at day 28, and patient satisfaction level were compared between the two groups. Results: Demographic, clinical variables and treatment received were comparable in the two groups. In the HFNC group, 90% of patients had successful outcomes with the initial oxygen therapy device used as compared with 56.6% in the NRBM group (p<0.001; odds ratio (OR) 0.145; 95% confidence interval (CI) 0.054 - 0.389). Using HFNC also resulted in improved oxygenation (PaO2 /FiO2 ) (p<0.001), better patient satisfaction (p<0.001), and a shorter time for de-escalation of oxygen therapy to a lower FiO2 device (p<0.001). The 28-day survival was higher in the HFNC group, but the difference was statistically insignificant (p=0.468). Conclusion: HFNC is a reliable oxygen therapy modality for moderate category COVID-19 pneumonia and results in a higher success rate of oxygen therapy, better oxygenation, and a greater patient satisfaction level as compared with a NRBM.

Molecular docking-based interactions in QSAR studies on Mycobacterium tuberculosis ATP synthase inhibitors.

Tuberculosis (TB) is a global threat with a large burden across the continents in terms of mortality, morbidity, and financial losses. The disease has evolved into multi-drug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) tuberculosis owing to numerous factors ranging from patients' non-compliance to demographical implications. There have been very few new drugs for resistant TB. Resistance has already been reported even for the newly introduced drug bedaquiline. An attempt has been made to integrate both structure-based and QSAR drug design techniques (QSAR-SBDD) for the identification of novel leads. The docking scores normally do not correlate with the activity. Hence, the docking results have been analysed in terms of the number of interactions rather than docking scores. The parameters derived from interactions have been used in developing the QSAR models. The best model shows a good correlation (r = 0.908) between the activity and interaction parameter 'C' describing the sum of all the interactions with each amino acid residue. This model also predicts external dataset with a good correlation (rext = 0.851) and can be used for the identification of novel chemical entities (NCEs) and repurposed drugs for TB therapeutics.

Effectiveness of a Cognitive Behavioral Randomized Controlled Trial for People Living with HIV Who are Heavy Drinkers: The Holistic Health Recovery Program (HHRP) Trial in Miami.

This study evaluates the impact of an intervention targeting high-risk behaviors among diverse, alcohol-using adults living with HIV (N = 267) from 2009 to 2013 in Miami, FL. The intervention took place in a group setting for eight sessions over 4 weeks and was compared to a didactic health promotion group. Assessments were conducted pre-intervention, post-intervention, and at 3, 6, and 12 months follow-up. Intervention participants (48% of sample) evidenced greater knowledge about HIV, more condom self-efficacy, and greater intentions to use condoms after participation. This was particularly noteworthy because associations among knowledge about HIV, more condom self-efficacy, and greater intentions to use condoms were negatively associated with intervention status at baseline. Participants also reported fewer heavy drinking days after participating in the intervention than those in the control group. Greater HIV knowledge, more condom self-efficacy and intentions to use condoms predicted more condom assertiveness; greater intentions to use condoms predicted fewer unprotected sexual behaviors. These findings underscore the importance of taking a comprehensive, multi-systemic approach to address risky behaviors in high-risk, diverse populations.

Measurement and memory in the periodically driven complex Ginzburg-Landau equation.

In the present work we illustrate that classical but nonlinear systems may possess features reminiscent of quantum ones, such as memory, upon suitable external perturbation. As our prototypical example, we use the two-dimensional complex Ginzburg-Landau equation in its vortex glass regime. We impose an external drive as a perturbation mimicking a quantum measurement protocol, with a given "measurement rate" (the rate of repetition of the drive) and "mixing rate" (characterized by the intensity of the drive). Using a variety of measures, we find that the system may or may not retain its coherence, statistically retrieving its original glass state, depending on the strength and periodicity of the perturbing field. The corresponding parametric regimes and the associated energy cascade mechanisms involving the dynamics of vortex waveforms and domain boundaries are discussed.

Percutaneous transplantation of allogenic bone marrow-derived mesenchymal stem cells for the management of paraplegia secondary to Hansen type I intervertebral disc herniation in a Beagle dog.

BACKGROUND: Intervertebral disc herniation (IVDH) is one of the common causes of spinal cord injury (SCI) in dogs. It is commonly treated by performing surgical decompression that involves the removal of the extruded disc material. However, the recovery rates after surgical interventions are variable and many times unsatisfactory. This report aims to document a case of paraplegia associated with IVDH in a Beagle dog and its therapeutic management using allogenic bone marrow-derived mesenchymal stem cells (aBM-MSCs). CASE DESCRIPTION: The dog was presented with paraplegia that was initiated three weeks back. Based on the findings of computed tomography (CT), the condition was diagnosed as Hansen type I IVDH at T12-T13 intervertebral space. FINDINGS/TREATMENT AND OUTCOME: Neurological examination was performed to grade the neurological deficit. The isolation, culture, and characterization of aBM-MSCs were done as per the standard protocol. The prepared cell suspension of aBM-MSCs was percutaneously transplanted to the spinal cord parenchyma at the site of injury. A total of four doses of 1 × 106 cells were given at an interval of 15 days along with methylcobalamin and gabapentin orally. Improvement was evaluated based on the neurological examination and grading. Considerable improvement was noticed after the first dose of aBM-MSCs. The animal started complete weight bearing on its pelvic limbs after two doses. CONCLUSION: Percutaneous transplantation of aBM-MSCs might have played an important role in reversing the neurological deficits secondary to IVDH in this dog. Further studies are required preferably in a larger population to confirm the efficacy of aBM-MSCs therapy in ameliorating neural deficits associated with IVDH.