Intralesional Bleomycin Versus Cryotherapy For Treatment Of Cutaneous Warts: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effectiveness of intralesional bleomycin in comparison to cryotherapy in the treatment of cutaneous warts. Methods: The randomized controlled trial was conducted at the Department of Dermatology, Jinnah Postgraduate Medical Centre, Karachi, from January to July 2021, and comprised patients of either gender aged 18-60 years who had cutaneous warts for 1-48 weeks. The subjects were divided into group A treated with 0.1% intralesional bleomycin, and group B were treated with cryotherapy through non probability consecutive sampling. Follow-up examination was done at the 2, 4 and 6 weeks. Data was analysed using SPSS 23. RESULTS: Of the 154 patients, 96(62.3%) were male and 58(37.7%) were females. The overall mean age was 33.253±6.726 years. There were 77(50%) patients in each of the two groups. The therapy after 6 weeks was found to be effective 73(94.8%). group A patients and 57(74%) group B patients (p=0.001). CONCLUSIONS: Intralesional bleomycin was found to be more successful than cryotherapy in the treatment of cutaneous warts.

Arabidopsis EARLY FLOWERING 3 controls temperature responsiveness of the circadian clock independently of the evening complex.

Daily changes in light and temperature are major entrainment cues that enable the circadian clock to generate internal biological rhythms that are synchronized with the external environment. With the average global temperature predicted to keep increasing, the intricate light-temperature coordination that is necessary for clock functionality is expected to be seriously affected. Hence, understanding how temperature signals are perceived by the circadian clock has become an important issue. In Arabidopsis, the clock component EARLY FLOWERING 3 (ELF3) not only serves as a light Zeitnehmer, but also functions as a thermosensor participating in thermomorphogenesis. However, the role of ELF3 in temperature entrainment of the circadian clock is not fully understood. Here, we report that ELF3 is essential for delivering temperature input to the clock. We demonstrate that in the absence of ELF3, the oscillator is unable to respond to temperature changes, resulting in an impaired gating of thermoresponses. Consequently, clock-controlled physiological processes such as rhythmic growth and cotyledon movement were disturbed. Genetic analyses suggest that the evening complex is not required for ELF3-controlled thermoresponsiveness. Together, our results reveal that ELF3 is an essential Zeitnehmer for temperature sensing of the oscillator, and thereby for coordinating the rhythmic control of thermoresponsive physiological outputs.

Photoperiod sensing of the circadian clock is controlled by EARLY FLOWERING 3 and GIGANTEA.

ELF3 and GI are two important components of the Arabidopsis circadian clock. They are not only essential for the oscillator function but are also pivotal in mediating light inputs to the oscillator. Lack of either results in a defective oscillator causing severely compromised output pathways, such as photoperiodic flowering and hypocotyl elongation. Although single loss of function mutants of ELF3 and GI have been well studied, their genetic interaction remains unclear. We generated an elf3 gi double mutant to study their genetic relationship in clock-controlled growth and phase transition phenotypes. We found that ELF3 and GI repress growth differentially during the night and the day, respectively. Circadian clock assays revealed that ELF3 and GI are essential that enable the oscillator to synchronize the endogenous cellular mechanisms to external environmental signals. In their absence, the circadian oscillator fails to synchronize to the light-dark cycles even under diurnal conditions. Consequently, clock-mediated photoperiod-responsive growth and development are completely lost in plants lacking both genes, suggesting that ELF3 and GI together convey photoperiod sensing to the central oscillator. Since ELF3 and GI are conserved across flowering plants and represent important breeding and domestication targets, our data highlight the possibility of developing photoperiod-insensitive crops by adjusting the allelic combination of these two key genes.

Genome-wide association study uncovers a novel QTL allele of AtS40-3 that affects the sex ratio of cyst nematodes in Arabidopsis.

Plant-parasitic cyst nematodes are obligate sedentary parasites that infect the roots of a broad range of host plants. Cyst nematodes are sexually dimorphic, but differentiation into male or female is strongly influenced by interactions with the host environment. Female populations typically predominate under favorable conditions, whereas male populations predominate under adverse conditions. Here, we performed a genome-wide association study (GWAS) in an Arabidopsis diversity panel to identify host loci underlying variation in susceptibility to cyst nematode infection. Three different susceptibility parameters were examined, with the aim of providing insights into the infection process, the number of females and males present in the infected plant, and the female-to-male sex ratio. GWAS results suggested that variation in sex ratio is associated with a novel quantitative trait locus allele on chromosome 4. Subsequent candidate genes and functional analyses revealed that a senescence-associated transcription factor, AtS40-3, and PPR may act in combination to influence nematode sex ratio. A detailed molecular characterization revealed that variation in nematode sex ratio was due to the disturbed common promoter of AtS40-3 and PPR genes. Additionally, single nucleotide polymorphisms in the coding sequence of AtS40-3 might contribute to the natural variation in nematode sex ratio.

Evaluation of effectiveness of a paediatric simulation course in procedural skills for paediatric residents - A pilot study.

OBJECTIVE: To explore the effects of simulation training on paediatric residents' confidence and skills in managing advanced skills in critical care. METHODS: The study was conducted at Alfaisal University, Riyadh, Saudi Arabia, from March to June 2016, and comprised junior residents in paediatrics. All paediatric residents (years 1 and 2) were recruited into two workshops, held one week apart. The first workshop covered lumbar puncture/ cerebrospinal fluid interpretation, oral intubation, bone marrow aspiration, and critical airway management. The second workshop covered chest tube insertion, pleural tap, insertion of central line, and arthrocentesis. The participants were surveyed using a 5-point Likert scale survey pre- and post-course, assessing their confidence. Their practical skills were assessed using a pre-objective structured clinical examination on the same day and post-course objective structured clinical examination a week later on selected skills. The outcome measures were: (1) pre-/post-course confidence rating, and (2) pre-/post-course objective structured clinical examination results. Data was analysed using SPSS 20. RESULTS: Of the 16 participants, 8(50%) were boys and 8(50%) girls. Besides, 13(81%) residents were in year-1 and 3(19%) in year-2. Median post-course confidence level ranks for all the skills were higher (p<0.05). There was no improvement in mean pre-objective structured clinical examination scores (2.31±2.66/ 7.46±3.02) and post- objective structured clinical examination scores (22.54±4.39/ 31.85±6.90) in Year 1 residents (p<0.001). CONCLUSIONS: Simulation course was significantly successful in improving residents' clinical skills and confidence in performing critical tasks.

Damage-associated responses of the host contribute to defence against cyst nematodes but not root-knot nematodes.

When nematodes invade and subsequently migrate within plant roots, they generate cell wall fragments (in the form of oligogalacturonides; OGs) that can act as damage-associated molecular patterns and activate host defence responses. However, the molecular mechanisms mediating damage responses in plant-nematode interactions remain unexplored. Here, we characterized the role of a group of cell wall receptor proteins in Arabidopsis, designated as polygalacturonase-inhibiting proteins (PGIPs), during infection with the cyst nematode Heterodera schachtii and the root-knot nematode Meloidogyne incognita. PGIPs are encoded by a family of two genes in Arabidopsis, and are involved in the formation of active OG elicitors. Our results show that PGIP gene expression is strongly induced in response to cyst nematode invasion of roots. Analyses of loss-of-function mutants and overexpression lines revealed that PGIP1 expression attenuates infection of host roots by cyst nematodes, but not root-knot nematodes. The PGIP1-mediated attenuation of cyst nematode infection involves the activation of plant camalexin and indole-glucosinolate pathways. These combined results provide new insights into the molecular mechanisms underlying plant damage perception and response pathways during infection by cyst and root-knot nematodes, and establishes the function of PGIP in plant resistance to cyst nematodes.

Role of Collagen Conduit With Duloxetine and/or Pregabalin in the Management of Partial Peripheral Nerve Injury.

PURPOSE: The objective of this study was to investigate the analgesic effect of a collagen conduit (Neuragen, Integra LifeSciences Corp, Plainsboro, NJ) using duloxetine (Cymbalta, Lilly, Indianapolis, IN) with or without pregabalin (Lyrica, Pfizer, NY) on pain induced by partial sciatic nerve transection in a rat model. MATERIAL AND METHODS: Adult male Sprague-Dawley rats were divided into 5 groups (n = 10 per group): group 1, nerve damage with no treatment; group 2, nerve damage treated with the application of a collagen conduit and saline; group 3, nerve damage treated with the application of a collagen conduit and duloxetine; group 4, nerve damage treated with the application of a collagen conduit and pregabalin; and group 5, nerve damage treated with the application of a collagen conduit and pregabalin plus duloxetine. Pain levels were evaluated by responses to mechanical and thermal stimuli at baseline before and 3 and 7 days after surgery. Interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF) levels were evaluated in blood, sciatic nerve, and dorsal root ganglion samples collected 7 days after surgery. RESULTS: The group treated with the collagen conduit and pregabalin exhibited markedly less pain 7 days postoperatively in response to mechanical and thermal stimuli compared with the other groups. IL-10 levels were considerably increased in the group treated with pregabalin. The groups treated with a collagen conduit and duloxetine and a combination of pregabalin and duloxetine also exhibited markedly less pain in response to mechanical and thermal stimuli 7 days after surgery compared with the group that had only nerve injury. The decrease in pain using duloxetine was not as robust but was associated with a decrease of TNF-α. The combination of pregabalin and duloxetine resulted in a substantial decrease in IL-6. CONCLUSION: Using a collagen conduit and duloxetine, pregabalin, and their combination helped alleviate neuropathic pain. The mechanism of action might be associated, at least in part, to cytokines.

An overview of natural variation studies in the Arabidopsis thaliana circadian clock.

Circadian clocks are ubiquitous mechanisms that provide an adaptive advantage by predicting subsequent environmental changes. In the model plant Arabidopsis thaliana (Arabidopsis), our understanding of the complex genetic network among clock components has considerably increased during these past years. Modeling has predicted the possibility of additional component to systematically and functionally complete the clock system. Mutagenesis screens have in the past been successfully employed to detect such novel components. With the advancement in sequencing technologies and improvements in statistical approaches, the extensive natural variation present in Arabidopsis accessions has emerged as a powerful alternative in functional gene discovery. In this review article, we review the previous efforts in mapping natural alleles affecting various clock parameters and will discuss further potentials of such natural-variation studies in physiological and ecological contexts.

Natural variants of ELF3 affect thermomorphogenesis by transcriptionally modulating PIF4-dependent auxin response genes.

BACKGROUND: Perception and transduction of temperature changes result in altered growth enabling plants to adapt to increased ambient temperature. While PHYTOCHROME-INTERACTING FACTOR4 (PIF4) has been identified as a major ambient temperature signaling hub, its upstream regulation seems complex and is poorly understood. Here, we exploited natural variation for thermo-responsive growth in Arabidopsis thaliana using quantitative trait locus (QTL) analysis. RESULTS: We identified GIRAFFE2.1, a major QTL explaining ~18 % of the phenotypic variation for temperature-induced hypocotyl elongation in the Bay-0 x Sha recombinant inbred line population. Transgenic complementation demonstrated that allelic variation in the circadian clock regulator EARLY FLOWERING3 (ELF3) is underlying this QTL. The source of variation could be allocated to a single nucleotide polymorphism in the ELF3 coding region, resulting in differential expression of PIF4 and its target genes, likely causing the observed natural variation in thermo-responsive growth. CONCLUSIONS: In combination with other recent studies, this work establishes the role of ELF3 in the ambient temperature signaling network. Natural variation of ELF3-mediated gating of PIF4 expression during nightly growing periods seems to be affected by a coding sequence quantitative trait nucleotide that confers a selective advantage in certain environments. In addition, natural ELF3 alleles seem to differentially integrate temperature and photoperiod information to induce architectural changes. Thus, ELF3 emerges as an essential coordinator of growth and development in response to diverse environmental cues and implicates ELF3 as an important target of adaptation.

A Guide to Quantify Arabidopsis Seedling Thermomorphogenesis at Single Timepoints and by Interval Monitoring.

Temperature-induced elongation of hypocotyls, petioles, and roots, together with hyponastic leaf responses, constitute key model phenotypes that can be used to assess a plant's capacity for thermomorphogenesis. Phenotypic responses are often quantified at a single time point during seedling development at different temperatures. However, to capture growth dynamics, several time points need to be assessed, and ideally continuous measurements are taken. Here we describe a general experimental setup and technical solutions for recording and measuring seedling phenotypes at single and multiple time points. Furthermore, we present an R-package called "rootdetectR," which allows easy processing of hypocotyl, root or petiole length, and growth rate data and provides different options of data presentation.

HIV, hepatitis B and hepatitis C in garbage scavengers of Karachi.

OBJECTIVES: To determine the seroprevalence of human immunodeficiency virus, hepatitis B and C, and to study the associated risk factors in garbage scavengers of Karachi. METHODS: The cross-sectional study was performed in a colony inhabited by low socioeconomic garbage-collecting people. Data was collected from April to December 2011. After informed consent and pre-test counselling, a set of questions were asked from a questionnaire, and 5cc of blood was drawn for pathological testing. SPSS 18 was used for statistical analysis. RESULTS: A total of 141 males agreed to participate in the study with a mean age of 21.33+/-9.28 years. Most of the respondents (n=67; 47.5%) were in the age group 11-20 years; 86 (61%) were single; 89 (63%) were illiterate and 127 (90%) had a monthly income less than Rs.10,000. Prevalence of hepatitis B was 18.8% (n=22), followed by 8.5% (n=10) and 0.85% (n=1) of hepatitis C and HIV respectively. Besides, 108 (77%) collected needles/syringes and 76 (54%) got pricked more than once. Only 23 (16%) wore gloves while collecting garbage. Overall, 79 (56%) had a history of sexual contact; 18 (23%) had three or more partners. CONCLUSION: The important factors contributing to the high prevalence of hepatitis B and C were needle prick injuries, bare-handed/bare-footed collection of garbage, poor vaccination status, improper garbage disposal system and the site of waste collection.

Frequency of conversion to overt hypothyroidism in patients with and without subclinical hypothyroidism.

BACKGROUND: Sub-clinical hypothyroidism (SCO) poses diagnostic and management difficulties for pathologists and clinicians. Cases of SCO are now diagnosed with increasing frequencies worldwide mainly because of availability of more sensitive methods for serum TSH, total T3 and free T4 assays. The rate of progression of SCO to overt hypothyroidism varies in different populations. Sub-clinical hypothyroidism has been suggested as a risk factor for hypothyroid complications. There is a need to identify and treat patients with SCO before they convert to overt hypothyroidism and develop complications. Objective was to compare the development of overt hypothyroidism in a cohort of patients of sub-clinical hypothyroidism and in subjects with normal thyroid function tests. METHODS: It was Cohort study conducted at Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi. Hundred patients of SCO and almost equal number of age and sex-matched subjects with normal Thyroid function test (TFT) were enrolled as healthy controls. Subclinical hypothyroid patients and controls were followed for a period of one year on six monthly bases. The patients were examined for signs and symptoms of hypothyroidism and serum TSH, total T3 and free T4 were estimated. The clinical history, physical examination and thyroid function tests were recorded on the pre-designed Performa. RESULTS: Fourteen (14%) out of 100 cases of the SCO patients developed overt hypothyroidism, SCO had 2.8 times more risk for conversion to overt hypothyroidism as compared to healthy controls. Moreover female gender and initial levels of serum TSH were the most important predictors for conversion of SCO to overt hypothyroidism. CONCLUSION: The frequency of conversion to overt hypothyroidism in SCO patients approaches 14% and was more commonly observed in female patients.

How to Detect QTLs in the Plant Circadian Clock.

One of the most powerful methods to identify loci controlling complex quantitative traits has been the quantitative trait locus (QTL) mapping. The QTL mapping approach has proven immensely useful to improve our understanding of key pathways such as flowering time, growth, and disease resistance. Since major circadian clock parameters such as period, phase, and amplitude are quantitative in nature, the QTL mapping approach could also be used to study the complex genetic architecture of the circadian clock. Here, we describe a simple QTL mapping method to identify components controlling clock parameters in natural populations of Arabidopsis thaliana.

Does foreign direct investment asymmetrically affect the mitigation of environmental degradation in Malaysia?

In this modern era, the global warming issue has been on the front burner of almost all countries including Malaysia. This study utilizing time series data spanning from 1970 to 2018. To this end, a linear and nonlinear autoregressive distributed lag model was conducted to reveal the foreign direct investment-growth-environment nexus. The conclusion validates the existence of the pollution haven hypothesis in Malaysia. Specifically, the empirical results of the linear autoregressive distributed lag model indicate that foreign direct investment and real gross domestic product have a significant positive impact on CO2 emission while carbon damage cost and the interaction term of foreign direct investment and carbon damage cost have a negative impact in the long run and short run. To find the asymmetric behavior of the foreign direct investment our study employed a nonlinear autoregressive distributed lag model. The findings confirmed the asymmetry association of foreign direct investment with CO2 emission. Interestingly, our results of the interaction term in both models are significant with a negative sign that shows the mediating effect of carbon damage cost that converts the positive effect of foreign direct investment on CO2 emission to negative. Thus, it is vital to reinforce the use of significant regulation as the Malaysian economy opens up to attract more foreign direct investment.

Haemophilus Parainfluenzae mural endocarditis with large atrial septal defect and peripheral embolization.

Mural endocarditis is a rare subclass of infective endocarditis (IE) associated with intra-cardiac tumors, prosthesis, valvular vegetation's, or structural abnormalities such as ventricular septal defects. Bacteria classified as HACEK (Haemophilus species, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae) are rare causes of IE found in only 1.3% to 10% of cases. We describe the second reported case of mural endocarditis involving the left ventricle (LV) caused by a Haemophilus species. A young male with no prior intravenous drug use, valvular heart disease, or recent dental work presented with splenic infarcts. H. para-influenza was identified on blood cultures. Cardiac imaging revealed a 1.5 cm LV mass underneath the posterior leaflet of the mitral valve and a large Atrial Septal Defect (ASD). Awaiting surgery, the patient sustained embolic and hemorrhagic cerebral events. The patient underwent debulking of LV mass, ASD closure, and mitral valve repair complicated by post-pericardiotomy syndrome, and he completed six weeks of ceftriaxone therapy. The patient met modified Duke Criteria, but the diagnosis was challenging due to absence of risk factors, sub-acute symptom onset, delayed blood culture growth, and ambiguous characterization of the mass on imaging. .

Aseptic meningitis after 20 years of endoscopic transsphenoidal pituitary surgery: a rare complication.

A transsphenoidal surgical (TSS) approach is used for pituitary gland surgery involving pituitary adenomas, as well as for the biopsy of various neurosurgical tumors. TSS, although a relatively safe procedure, can lead to complications like hypopituitarism, visual impairment, nasal septal perforation, diabetes insipidus, carotid artery injury, and cerebrospinal fluid (CSF) leaks. Aseptic meningitis is also one of the complications of this procedure with an incidence of 1-2%, presenting with symptoms similar to bacterial meningitis, but with a low-grade fever of <102 F or even apyrexia. Here, we present a rare case of aseptic meningitis due to CSF leakage, presenting after 20 years of endoscopic surgery. A ventriculoperitoneal shunt was placed to stem the leak after two unsuccessful attempts of endonasal repair.

Clinical implications of Type 2 diabetes on outcomes after cardiac transplantation.

BACKGROUND: T2D is an increasingly common disease that is associated with worse outcomes in patients with heart failure. Despite this, no contemporary study has assessed its impact on heart transplantation outcomes. This paper examines the demographics and outcomes of patients with type 2 diabetes (T2D) undergoing heart transplantation. METHODS: Using the United Network for Organ Sharing (UNOS) database, patients listed for transplant were separated into cohorts based on history of T2D. Demographics and comorbidities were compared, and cox regressions were used to examine outcomes. RESULTS: Between January 1st, 2011 and June 12th, 2020, we identified 9,086 patients with T2D and 23,676 without T2D listed for transplant. The proportion of patients with T2D increased from 25.2% to 27.9% between 2011 and 2020. Patients with T2D were older, more likely to be male, less likely to be White, and more likely to pay with public insurance (p<0.001, all). After adjustment, T2D patients had a lower likelihood of transplantation (Hazard Ratio [HR]: 0.93, CI: 0.90-0.96, p<0.001) and a higher likelihood of post-transplant mortality (HR: 1.30, CI: 1.20-1.40, p<0.001). Patients with T2D were more likely to be transplanted in the new allocation system compared to the old allocation system (all, p<0.001). CONCLUSIONS: Over the last ten years, the proportion of heart transplant recipients with T2D has increased. These patients are more likely to be from traditionally underserved populations. Patients with T2D have a lower likelihood of transplantation and a higher likelihood of post-transplant mortality. After the allocation system change, likelihood of transplantation has improved for patients with T2D.

Mechanical ventilation at the time of heart transplantation and associations with clinical outcomes.

AIMS: The impact of mechanical ventilation (MV) at the time of heart transplantation is not well understood. In addition, MV was recently removed as a criterion from the new US heart transplantation allocation system. We sought to assess for the association between MV at transplantation and 1-year mortality. METHODS AND RESULTS: We utilized the United Network for Organ Sharing database and included all adult, single organ heart transplantations from 1990 to 2019. We utilized multivariable logistic regression adjusting for demographics, comorbidities, and markers of clinical acuity. We identified 60 980 patients who underwent heart transplantation, 2.4% (n = 1431) of which required MV at transplantation. Ventilated patients were more likely to require temporary mechanical support, previous dialysis, and had a shorter median waitlist time (21 vs. 95 days, P < 0.001). At 1 year, the mortality was 33.7% (n = 484) for ventilated patients and 11.7% (n = 6967) for those not ventilated at the time of transplantation (log-rank P < 0.001). After multivariable adjustment, patients requiring MV continued to have a substantially higher 90-day [odds ratio (OR) 3.20, 95% confidence interval (CI): 2.79-3.66, P < 0.001] and 1-year mortality (OR 2.67, 95% CI: 2.36-3.03, P < 0.001). For those that survived to 90 days, the adjusted mortality at 1 year continued to be higher (OR 1.48, 95% CI: 1.16-1.89, P = 0.002). CONCLUSION: We found a strong association between the presence of MV at heart transplantation and 90-day and 1-year mortality. Future studies are needed to identify which patients requiring MV have reasonable outcomes, and which are associated with substantially poorer outcomes.

Impact of disasters, including pandemics, on cardiometabolic outcomes across the life-course: a systematic review.

BACKGROUND: Disasters are events that disrupt the daily functioning of a community or society, and may increase long-term risk of adverse cardiometabolic outcomes, including cardiovascular disease, obesity and diabetes. The objective of this study was to conduct a systematic review to determine the impact of disasters, including pandemics, on cardiometabolic outcomes across the life-course. DESIGN: A systematic search was conducted in May 2020 using two electronic databases, EMBASE and Medline. All studies were screened in duplicate at title and abstract, and full-text level. Studies were eligible for inclusion if they assessed the association between a population-level or community disaster and cardiometabolic outcomes ≥1 month following the disaster. There were no restrictions on age, year of publication, country or population. Data were extracted on study characteristics, exposure (eg, type of disaster, region, year), cardiometabolic outcomes and measures of effect. Study quality was evaluated using the Joanna Briggs Institute critical appraisal tools. RESULTS: A total of 58 studies were included, with 24 studies reporting the effects of exposure to disaster during pregnancy/childhood and 34 studies reporting the effects of exposure during adulthood. Studies included exposure to natural (n=35; 60%) and human-made (n=23; 40%) disasters, with only three (5%) of these studies evaluating previous pandemics. Most studies reported increased cardiometabolic risk, including increased cardiovascular disease incidence or mortality, diabetes and obesity, but not all. Few studies evaluated the biological mechanisms or high-risk subgroups that may be at a greater risk of negative health outcomes following disasters. CONCLUSIONS: The findings from this study suggest that the burden of disasters extend beyond the known direct harm, and attention is needed on the detrimental indirect long-term effects on cardiometabolic health. Given the current COVID-19 pandemic, these findings may inform public health prevention strategies to mitigate the impact of future cardiometabolic risk. PROSPERO REGISTRATION NUMBER: CRD42020186074.