A review of efficacy and safety of Ugandan anti-malarial plants with application of RITAM score.

BACKGROUND: Malaria, a treatable disease mainly caused by Plasmodium falciparum has remained a health challenge in Africa, a continent that accounted for 96% of total global cases and deaths in 2021. Uganda, a malaria endemic country is experiencing malaria parasite resistance to some of the drugs used in the artemisinin-based combination therapy (ACT). In an effort to prioritize herbal medicines for new product development, this review synthesized the available safety and efficacy literature on the Ugandan anti-malarial plants to suggest most effective herbal plants. METHODS: Literature was exhaustively searched using engines and databases, such as Google scholar, Pubmed, and Scopus-indexed journals during the period of June 2020-December 2021. In the first phase, information on ethnobotanical uses of anti-malarial plants in Uganda was gathered and synthetized to generate a list of plants, followed by data on anti-malarial efficacy (both in vitro and in vivo) on each listed plant. Minimum inhibitory concentrations (µg/ml), and % parasite suppression for every plant were scored using The Research Initiative on Traditional and Antimalarial Methods (RITAM) scoring system. The best twenty (20) plants were evaluated for acute safety (LD50) data in rat model, plant parts used, ease of cultivation, presence of clinical studies and other relevant factors for suggesting the best three (3) plants for future anti-malarial product development. RESULTS: Over one hundred twenty-six (126) plant species are used in Uganda for treatment of malaria in local communities. Out of these, about 33% (41) have been studied for efficacy and safety, with Artemisia annua and Vernonia amygdalina being the most extensively studied and among the best twenty (20) anti-malarial plants in Uganda. Both are limited by parasite recrudescence in clinical studies. Microglossa pyrifolia, a very potent plant (IC50 = 0.03 - 0.05 µg/ml has potential to penetrate the liver and could ameliorate the challenge of recrudescence if combined with A. annua and V. amygdalina in a polyherbal formulation. CONCLUSION: There are many plants with promising potential for malaria treatment in Uganda and a herbal combination of A. annua, V. amydalina and M. pyrifolia could offer the next herbal ACT if carefully studied and developed.

Cutaneous Leishmaniasis Emergence in Southeastern Mexico: The Case of the State of Yucatan.

Environmental changes triggered by deforestation, urban expansion and climate change are present-day drivers of the emergence and reemergence of leishmaniasis. This review describes the current epidemiological scenario and the feasible influence of environmental changes on disease occurrence in the state of Yucatan, Mexico. Relevant literature was accessed through different databases, including PubMed, Scopus, Google, and Mexican official morbidity databases. Recent LCL autochthonous cases, potential vector sandflies and mammal hosts/reservoirs also have been reported in several localities of Yucatan without previous historical records of the disease. The impact of deforestation, urban expansion and projections on climate change have been documented. The current evidence of the relationships between the components of the transmission cycle, the disease occurrence, and the environmental changes on the leishmaniasis emergence in the state shows the need for strength and an update to the intervention and control strategies through a One Health perspective.

Leishmania (Leishmania) mexicana Infection in Wild Rodents from an Emergent Focus of Cutaneous Leishmaniasis in Yucatan, Mexico.

In 2015, emergent cases of localized cutaneous leishmaniasis (LCL) were reported in Tinum, Yucatan, Mexico. As part of an eco-epidemiological study to characterize the elements that trigger Leishmania infection in that area, we conducted a field study to investigate the occurrence of Leishmania infection in wild rodents. From November 2019 to February 2020, rodents were caught from three sites located in the municipality of Tinum, Yucatan. For each specimen, clinical signs suggestive of Leishmania infection were recorded. Samples from the tail, liver, and spleen were taken for the identification of Leishmania DNA by PCR. Twenty rodents belonging to two species were caught including Heteromys gaumeri (55%, 11/20) and Ototylomys phyllotis (45%, 9/20). Fifty-five percent of the animals presented white spots on the tail, 15% had splenomegaly, and 5% had hepatomegaly. Fifty-five percent (11/20) of the animals were found infected by Leishmania. Heteromys gaumeri was caught in all trapping sites and was the most infected species (63.6%, 7/11). The percentage of infection for O. phyllotis was 44.4% (4/9). Leishmania (Leishmania) mexicana was identified as the infecting species in two H. gaumeri. This study provides, for the first time, evidence of Leishmania infection in wild rodents from the Yucatan state. Heteromys gaumeri and O. phyllotis may be involved in the transmission cycle of L. mexicana in this emergent focus; however, further longitudinal studies are needed to confirm their role as primary reservoirs.

Tropical tree mortality has increased with rising atmospheric water stress.

Evidence exists that tree mortality is accelerating in some regions of the tropics1,2, with profound consequences for the future of the tropical carbon sink and the global anthropogenic carbon budget left to limit peak global warming below 2 °C. However, the mechanisms that may be driving such mortality changes and whether particular species are especially vulnerable remain unclear3-8. Here we analyse a 49-year record of tree dynamics from 24 old-growth forest plots encompassing a broad climatic gradient across the Australian moist tropics and find that annual tree mortality risk has, on average, doubled across all plots and species over the last 35 years, indicating a potential halving in life expectancy and carbon residence time. Associated losses in biomass were not offset by gains from growth and recruitment. Plots in less moist local climates presented higher average mortality risk, but local mean climate did not predict the pace of temporal increase in mortality risk. Species varied in the trajectories of their mortality risk, with the highest average risk found nearer to the upper end of the atmospheric vapour pressure deficit niches of species. A long-term increase in vapour pressure deficit was evident across the region, suggesting that thresholds involving atmospheric water stress, driven by global warming, may be a primary cause of increasing tree mortality in moist tropical forests.

Use of Convalescent Plasma Therapy with Best Available Treatment (BAT) among Hospitalized COVID-19 Patients: A Multi-Center Study

The COVID-19 disease caused by SARS-CoV2 virus has gripped the whole world with overwhelming strain in our health system. Currently, there are no standard guidelines in its treatment but the possible benefits of convalescent plasma in limiting complications and severity of the COVID-19 disease have emerged. OBJECTIVEThis study aims to determine the effectiveness and safety of using convalescent plasma in improving the clinical course of hospitalized patients diagnosed with COVID-19 disease admitted at University of Santo Tomas and Makati Medical Center. METHODSThis study is a quasi-experimental (prospective analytical), and multi-center study involving 65 patients diagnosed with COVID-19 Disease who received convalescent plasma, with 65 patients who only received best available treatment serving as age-gender-matched control. RESULTSMedian age of the population who received convalescent plasma was 60 years old, mostly male (68%), and manifested severe pneumonia (47%). There was noted statistically signifcant decrease between the pre-and post-treatment values of hemoglobin (p=0.04) and LDH (p=0.086). There was also statistically significant increase in platelet counts (p=0.01). WBC and PaO2 increased while ferritin and PFR decreased after convalescent plasma transfusion, however, these were not statistically significant. Length of stay and clinical outcome of those who received convalescent plasma were then compared to age-gender matched controls who only received best available treatment. There was noted statistically significant difference between length of stay (p=0.00) among those who received convalescent plasma as compared to those who did not. This was seen across severe and critically ill COVID-19 patients. There was also more mortality seen in the best available treatment alone group, but this was non-significant. CONCLUSIONSConvalescent plasma use showed no significant impact in the recovery rate and outcome of patients who received it as compared to those who did not, however, its use was proven to be safe among all patients regardless of the level of severity and clinical profile.

Cardiometabolic Disease Burden and Steroid Excretion in Benign Adrenal Tumors : A Cross-Sectional Multicenter Study.

BACKGROUND: Benign adrenal tumors are commonly discovered on cross-sectional imaging. Mild autonomous cortisol secretion (MACS) is regularly diagnosed, but its effect on cardiometabolic disease in affected persons is ill defined. OBJECTIVE: To determine cardiometabolic disease burden and steroid excretion in persons with benign adrenal tumors with and without MACS. DESIGN: Cross-sectional study. SETTING: 14 endocrine secondary and tertiary care centers (recruitment from 2011 to 2016). PARTICIPANTS: 1305 prospectively recruited persons with benign adrenal tumors. MEASUREMENTS: Cortisol excess was defined by clinical assessment and the 1-mg overnight dexamethasone-suppression test (serum cortisol: <50 nmol/L, nonfunctioning adrenal tumor [NFAT]; 50 to 138 nmol/L, possible MACS [MACS-1]; >138 nmol/L and absence of typical clinical Cushing syndrome [CS] features, definitive MACS [MACS-2]). Net steroid production was assessed by multisteroid profiling of 24-hour urine by tandem mass spectrometry. RESULTS: Of the 1305 participants, 49.7% had NFAT (n = 649; 64.1% women), 34.6% had MACS-1 (n = 451; 67.2% women), 10.7% had MACS-2 (n = 140; 73.6% women), and 5.0% had CS (n = 65; 86.2% women). Prevalence and severity of hypertension were higher in MACS-2 and CS than NFAT (adjusted prevalence ratios [aPRs] for hypertension: MACS-2, 1.15 [95% CI, 1.04 to 1.27], and CS, 1.37 [CI, 1.16 to 1.62]; aPRs for use of ≥3 antihypertensives: MACS-2, 1.31 [CI, 1.02 to 1.68], and CS, 2.22 [CI, 1.62 to 3.05]). Type 2 diabetes was more prevalent in CS than NFAT (aPR, 1.62 [CI, 1.08 to 2.42]) and more likely to require insulin therapy for MACS-2 (aPR, 1.89 [CI, 1.01 to 3.52]) and CS (aPR, 3.06 [CI, 1.60 to 5.85]). Urinary multisteroid profiling revealed an increase in glucocorticoid excretion from NFAT over MACS-1 and MACS-2 to CS, whereas androgen excretion decreased. LIMITATIONS: Cross-sectional design; possible selection bias. CONCLUSION: A cardiometabolic risk condition, MACS predominantly affects women and warrants regular assessment for hypertension and type 2 diabetes. PRIMARY FUNDING SOURCE: Diabetes UK, the European Commission, U.K. Medical Research Council, the U.K. Academy of Medical Sciences, the Wellcome Trust, the U.K. National Institute for Health Research, the U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.

Tropical tree growth sensitivity to climate is driven by species intrinsic growth rate and leaf traits.

A better understanding of how climate affects growth in tree species is essential for improved predictions of forest dynamics under climate change. Long-term climate averages (mean climate) drive spatial variations in species' baseline growth rates, whereas deviations from these averages over time (anomalies) can create growth variation around the local baseline. However, the rarity of long-term tree census data spanning climatic gradients has so far limited our understanding of their respective role, especially in tropical systems. Furthermore, tree growth sensitivity to climate is likely to vary widely among species, and the ecological strategies underlying these differences remain poorly understood. Here, we utilize an exceptional dataset of 49 years of growth data for 509 tree species across 23 tropical rainforest plots along a climatic gradient to examine how multiannual tree growth responds to both climate means and anomalies, and how species' functional traits mediate these growth responses to climate. We show that anomalous increases in atmospheric evaporative demand and solar radiation consistently reduced tree growth. Drier forests and fast-growing species were more sensitive to water stress anomalies. In addition, species traits related to water use and photosynthesis partly explained differences in growth sensitivity to both climate means and anomalies. Our study demonstrates that both climate means and anomalies shape tree growth in tropical forests and that species traits can provide insights into understanding these demographic responses to climate change, offering a promising way forward to forecast tropical forest dynamics under different climate trajectories.

Demographic, Behavioral, and Clinical Characteristics of Persons Seeking Care at Sexually Transmitted Disease Clinics - 14 Sites, STD Surveillance Network, United States, 2010-2018.

PROBLEM: Sexually transmitted diseases (STDs) are a major cause of morbidity in the United States, with an estimated $15.9 billion in lifetime direct medical costs. Although the majority of STDs are diagnosed in the private sector, publicly funded STD clinics have an important role in providing comprehensive sexual health care services, including STD and HIV screening, for a broad range of patients. In certain cases, STD clinics often are the only source of sexual health care for patients, particularly among gay, bisexual, and other men who have sex with men (MSM). PERIOD COVERED: 2010-2018. DESCRIPTION OF THE SYSTEM: The STD Surveillance Network (SSuN) is an ongoing sentinel surveillance system for monitoring clinical information among patients attending STD clinics. SSuN is a collaboration of competitively selected state and city health departments that conduct facility-based sentinel surveillance in STD clinics. Information routinely collected through the course of patient encounters is obtained for all patients seeking care in the participating STD clinics. This information includes demographic, behavioral, and clinical characteristics (e.g., STD and HIV tests performed and STD and HIV diagnoses). This report presents 2010-2018 SSuN data from 14 STD clinics in five cities (Baltimore, Maryland; New York City, New York; Philadelphia, Pennsylvania; San Francisco, California; and Seattle, Washington) to describe the patient populations seeking care in these STD clinics. Estimated numbers and percentages of patients receiving selected STD-related health services were calculated for each year by using an inverse variance weighted random-effects model, adjusting for heterogeneity among SSuN jurisdictions. Trends in receipt of selected STD-related health services were examined and included HIV screening after an acute STD diagnosis among persons not previously known to have HIV infection, annual chlamydia screening among adolescent and young females, and extragenital chlamydia and gonorrhea screening among MSM. RESULTS: During 2010-2018, the total number of annual visits made in the 14 participating STD clinics decreased 29.8% (from 145,728 to 102,275 visits), and the total number of unique patients examined in the clinics decreased 35.1% (from 94,281 to 61,172 patients). Decreases in the number of unique patients occurred both among men who have sex with women only (42.4%; from 37,842 in 2010 to 21,781 in 2018) and among females (51.4%; from 36,485 in 2010 to 17,721 in 2018). The decreases in the number of female patients were observed across all age groups, although they were more pronounced among females aged ≤24 years (66.4%; from 17,721 in 2010 to 5,962 in 2018). In contrast, the number of patients identified as MSM increased 44.0% (from 12,859 in 2010 to 18,512 in 2018), with the greatest increase among MSM aged ≥25 years (58.6%; from 9,918 in 2010 to 15,733 in 2018). Among visits during which an acute STD (defined as chlamydia, gonorrhea, or primary or secondary syphilis) was diagnosed, the percentage of visits during which an HIV test was performed within approximately 14 days of the STD diagnosis increased from 58.2% in 2010 to 70.2% in 2018. Among those patients tested, 1,672 HIV infections were identified, of which 84.0% were among MSM. Among females aged 15-24 years, the percentage screened for chlamydia in any calendar year increased from 88.6% in 2010 to 90.6% in 2018. However, because fewer females aged 15-24 years attended these clinics during the study period, the crude number of adolescent and young females tested for chlamydia decreased from 14,249 in 2010 to 4,507 in 2018. During 2010-2018, the percentage of females retested after their first positive chlamydia diagnosis during the same year ranged from 11.4% to 13.3%. During 2010-2018, the percentage of MSM tested for rectal chlamydia and rectal gonorrhea increased (from 54.7% to 57.8% and from 55.0% to 58.4%, respectively). During the same period, increases were noted in the percentage of MSM with diagnosed rectal chlamydia (from 15.5% in 2010 to 17.7% in 2018) and rectal gonorrhea (from 13.3% in 2010 to 17.1% in 2018). In contrast with pharyngeal chlamydia, pharyngeal gonorrhea screening was more common (from 69.5% in 2010 to 74.6% in 2018), and the percentage positive doubled during the study period (from 7.3% in 2010 to 14.8% in 2018). Pharyngeal chlamydia testing also increased (from 50.3% in 2010 to 72.9% in 2018), with concurrent decreases in positivity (from 4.2% in 2010 to 2.6% in 2018). INTERPRETATION: During 2010-2018, changes occurred in the demographic composition of patients attending STD clinics participating in SSuN. Understanding trends in the demographic profile of STD patients and services provided can help identify addressable gaps in STD control efforts and direct public health action. Overall, fewer females, especially those aged 15-24 years, accessed care in these STD clinics during the study period. Untreated STDs among adolescent and young females can have serious consequences, including pelvic inflammatory disease and infertility. Additional efforts to monitor where adolescent and young females seek care and to ensure they are receiving quality STD-related health services are needed, especially considering increases in reported cases of STDs among females. Increases in the number of MSM attending STD clinics present a unique opportunity to reach this population with STD and HIV prevention services. Although a large percentage of STD cases are diagnosed outside of STD clinics, publicly funded STD clinics are an important safety-net provider of STD-related health services and provide vital STD-related health services for patient populations at risk for the consequences of STDs and HIV infection. PUBLIC HEALTH ACTIONS: STD-related health services represent effective strategies for preventing STD and HIV transmission and acquisition or STD-related sequelae. Ensuring that all persons receive quality HIV and STD prevention and treatment services is vital for an effective public health approach to reducing STDs. STD clinics provide crucial safety-net services for preventing STD-related morbidity, including timely identification and treatment of curable STDs such as chlamydia, gonorrhea, and syphilis. Increases in the numbers of MSM attending STD clinics participating in SSuN provide additional opportunities for linking patients to high-impact HIV preventive services (e.g., pre-exposure prophylaxis), and the clinics are positioned to facilitate initiation or resumption of treatment among persons living with HIV.

First report and molecular identification of Trypanosoma (Duttonella) vivax outbreak in cattle population from Ecuador.

The bovine trypanosomosis is responsible for economic losses from tropical and subtropical areas of Africa and Latin America. This disease is characterized by fever, anaemia, loss of production and even death. Few studies have been carried out in Ecuador regarding Trypanosoma spp. presence but the species has not been determined in cattle and those have only determined the presence of genus, but not the species. The aim of this study was to identify and characterize the trypanosome species involved in the suspected bovine trypanosomosis outbreak reported in Convento Village in Manabí Province located in the coastal region of Ecuador. Twenty cattle from three farms were sampled. Three samples were positive for T. vivax, using an end-point polymerase chain reaction (PCR) to amplify a fragment of the cathepsin L-like cysteine protease (CatL-like) gene. A phylogenetic tree analysis of these three Ecuadorian isolates showed a close relationship with isolates from South America (Colombia, Brazil and Venezuela) and West Africa (Nigeria). This is the first report of T. vivax in Ecuadorian cattle.

Physical Activity Is Associated With Better Vascular Function in Children and Adolescents With Congenital Heart Disease.

BACKGROUND: Aortic stiffness is an important marker of cardiovascular risk and is elevated in children and adolescents with congenital heart disease (CHD) compared with healthy children; however, in children with CHD, little is known about the interaction between aortic stiffness and physical activity-a key determinant of aortic stiffness. METHODS: For this cross-sectional cohort study, we recruited children and adolescents aged 9-16 years with moderate-to-complex CHD from British Columbia Children's Hospital and travelling partnership clinics across the province of British Columbia and the Yukon territory. Mean daily minutes of moderate-to-vigorous physical activity were objectively assessed using an ActiGraph accelerometer worn over the right hip during waking hours for 7 days. Aortic pulse wave velocity (cm/s) was measured using standard 2-dimensional echocardiography and Doppler ultrasound. RESULTS: Participants (n = 104, 61% male; 85% consent rate) had a mean (standard deviation) age of 12.4 (2.4) years. Daily moderate-to-vigorous physical activity was 46.7 (20.0) minutes/d, with 25% meeting guidelines of ≥ 60 minutes of moderate-to-vigorous physical activity per day. Mean (standard deviation) aortic pulse wave velocity was 490.5 (161.9) cm/s, which was not significantly different between cardiac diagnoses. Higher levels of moderate-to-vigorous physical activity were associated with lower aortic pulse wave velocity (r = -0.226, P = 0.021). CONCLUSION: In children and adolescents with CHD, higher levels of physical activity are associated with better vascular function. Given this association, promoting physical activity should be a high priority in the care of children and adolescents with CHD.

Dynamic Internal Jugular Vein Compression by Hypertrophic Hyoid Bone: Management and Outcomes.

Extracranial osseous compression of the internal jugular vein (IJV) is exceedingly rare. The clinical manifestations of IJV obstruction are very heterogeneous and subtle, and arriving at a diagnosis can be challenging. We describe a case of dynamic IJV compression in a 40-year-old male with progressive, positional, ill-defined right periorbital and neck pain associated with photosensitivity. Imaging showed a hypertrophic right hyoid bone; computed tomography venogram (CTV) with challenging maneuvers demonstrated dynamic compression of the ipsilateral IJV by a hypertrophied hyoid bone and thyroid cartilage. The patient underwent decompression of the right jugular vein which resulted in the resolution of his symptoms. The clinical manifestations of extracranial IJV impingement are variable and diagnostically challenging. Disturbances in extracranial IJV outflow is a diagnosis of exclusion and could be responsible for atypical facial pain in a select group of patients. This entity should be considered in the differential of atypical facial, especially when symptoms tend to be positional.

Recurrent Stroke in Giant Cell Arteritis Despite Immunotherapy.

OBJECTIVE: To describe rare but important cerebrovascular complications of giant cell arteritis (GCA). CASE REPORT: We report a 59-year-old man who initially presented with vasculitis of the lower extremities. While on steroids, he developed strokes in multiple vascular territories. The conventional angiogram showed stenosis of bilateral carotid and vertebral vessels as they entered the dura. Temporal artery biopsy confirmed GCA. He began cyclophosphamide treatment, which stabilized his clinical course; however, this was switched to tocilizumab by an outside rheumatologist. Two months later, the patient had progression of vessel stenosis and suffered additional strokes. Despite interventions to augment cerebral perfusion, the infarctions continued to expand and the patient passed away. CONCLUSIONS: This case highlights several important features of strokes in GCA: the predilection for the dural entry point of cerebral blood vessels, the progression of disease despite steroids, and the need to quickly escalate treatment in these cases. As seen in our patient, however, this disease carries high morbidity and mortality and patients often have poor outcomes despite aggressive immunosuppression.

Long-Term Outcomes of a Phase 2 Trial of Chemotherapy With Consolidative Radiation Therapy for Oligometastatic Non-Small Cell Lung Cancer.

PURPOSE: Recent data indicate consolidative radiation therapy improves progression-free survival (PFS) for patients with oligometastatic non-small cell lung cancer (NSCLC). Data on long-term outcomes are limited. METHODS AND MATERIALS: This prospective, multicenter, single-arm, phase 2 trial was initiated in 2010 and enrolled patients with oligometastatic NSCLC. Oligometastatic disease was defined as a maximum of 5 metastatic lesions for all disease sites, including no more than 3 active extracranial metastatic lesions. Limited mediastinal lymph node involvement was allowed. Patients achieving a partial response or stable disease after 3 to 6 cycles of platinum-based chemotherapy were treated with CRT to the primary and metastatic sites of disease, followed by observation alone. The primary endpoint was PFS, with secondary endpoints of local control, overall survival (OS), and safety. RESULTS: Twenty-nine patients were enrolled between October 2010 and October 2015, and 27 were eligible for consolidative radiation therapy. The study was closed early because of slow accrual but met its primary endpoint for success, which was PFS >6 months (P < .0001). The median PFS (95% confidence interval) was 11.2 months (7.6-15.9 months), and the median OS was 28.4 months (14.5-45.8 months). Survival outcomes were not significantly different for patients with brain metastases (P = .87 for PFS; P = .12 for OS) or lymph node involvement (P = .74 for PFS; P = .86 for OS). CONCLUSIONS: For patients with oligometastatic NSCLC, chemotherapy followed by consolidative radiation therapy without maintenance chemotherapy was associated with encouraging long-term outcomes.

Ascending Spinal Cord Infarction Secondary to Recurrent Spinal Cord Cavernous Malformation Hemorrhage.

We report a case of a 58-year-old Hispanic man who developed ascending paraparesis over several weeks secondary to recurrent hemorrhages and resulting in spinal cord ischemia from a low thoracic spinal cord cavernous malformation. The patient's deterioration was attributed to recurrent hemorrhage of a thoracic intramedullary cavernous malformation at T11 resulting in vascular congestion and spinal cord ischemia. The patient was found to have a heterozygous mutation on exon 13 of gene KRIT1, which was consistent with autosomal dominant familial cerebral cavernous malformations. Expedited surgical intervention potentially could have prevented this patient's progressive paraplegia.

Bulbar conjunctival microvascular responses in dry eye.

PURPOSE: Conjunctival microvascular responses may be a surrogate metric of efferent neural pathway function innervating the ocular surface as changes in blood flow occur within seconds after a stimulus. As somatosensory dysfunction may partially underlie dry eye (DE), in this study we evaluate whether bulbar conjunctival microvascular alterations correlate with various aspects of DE. METHODS: Fifty-six DE patients were prospectively recruited from a Veterans Affairs ophthalmology clinic over an 11-month period. DE symptoms and ocular pain were assessed along with DE signs. A novel functional slit lamp biomicroscope (FSLB) was used to image the temporal bulbar conjunctiva from the right eye before and after central corneal stimulation with an air puff. Blood flow velocities were measured and noninvasive microvascular perfusion maps (nMPMs) were created. RESULTS: The bulbar blood flow velocity was 0.50 ± 0.15 mm/s at baseline and increased to 0.55 ± 0.17 mm/s after stimulation (P < 0.001); the average change in velocity was 0.05 ± 0.09. nMPMs values and venule diameter, on the other hand, did not significantly increase after stimulation (1.64 ± 0.004 at baseline, 1.65 ± 0.04 after stimulation, P = 0.22 and 22.13 ± 1.84 µm at baseline, 22.21 ± 2.04 µm after stimulation, P = 0.73, respectively). Baseline blood flow velocity positively associated with Schirmer scores (r = 0.40, P = 0.002). Those with higher self-rated wind hyperalgesia demonstrated less change in blood flow velocity (r = -0.268, P = 0.046) after air stimulation on the central cornea. CONCLUSION: Conjunctival blood flow velocity, but not vessel diameter or complexity, increases after wind stimuli. Baseline flow positively correlated with Schirmer scores while change in flow negatively correlated with self-reported wind hyperalgesia.

Looking for PANDAS in Missouri.

This review seeks to educate clinicians and advocate for patients having acute-onset pediatric autoimmune encephalopathy. Primary care providers caring for children are not fully aware of the debilitating illness that changes the life of a child and a family overnight. Our goal is to heighten awareness of a) the initial diagnosis, b) treatment and c) information about referral of affected children by health professionals in Missouri and surrounding states.

Minocycline-induced polyarteritis nodosa-like vasculitis presenting as brainstem stroke.

Minocycline use has been associated with the development of autoimmune disorders, including drug-induced vasculitis. Previously published reports suggest that clinical manifestations are limited to cutaneous, constitutional, or musculoskeletal symptoms. To our knowledge there has been only one reported patient with ischemic stroke in the setting of minocycline-induced vasculitis. We describe a 26-year-old woman, with no vascular risk factors, who had an ischemic pontine stroke in the setting of biopsy-proven minocycline-induced polyarteritis nodosa-like vasculitis. Discontinuation of minocycline resulted in resolution of the vasculitis, and she has not had any recurrent ischemic events. This report shows that ischemic strokes may occur as a result of minocycline-induced vasculitis. While this is likely a rare association, recognition is important given the widespread use of minocycline and the potential for devastating consequences in a young population. Consequently, drug-induced vasculitis should be considered in patients with an ischemic stroke taking minocycline.

Grafting Using Rootstocks with Resistance to Ralstonia solanacearum Against Meloidogyne incognita in Tomato Production.

Root-knot nematodes (RKNs; Meloidogyne spp.) and Ralstonia solanacearum, the causal agent of bacterial wilt, are major soilborne pathogens in U.S. tomato production. Methyl bromide has been used for decades to effectively manage RKN but its phase-out and the high cost of other effective fumigants such as 1,3-dichloropropene has resulted in a need to develop sustainable alternatives. Many of the commercially popular varieties used by the tomato industry do not have resistance to RKNs and R. solanacearum. Recent studies worldwide have shown the potential for grafting using resistant rootstocks as a sustainable and ecofriendly practice for R. solanacearum management. However, the effectiveness of R. solanacearum-resistant rootstocks on RKN management is not known. In this study, three commercially available R. solanacearum-resistant tomato rootstocks ('RST-04-106-T', 'BHN 998', and 'BHN 1054') were evaluated for resistance to Meloidogyne incognita in field tomato production in four field trials conducted for two consecutive years in two geographical locations: Florida and Virginia. Grafting rootstocks onto 'BHN 602' a tomato scion susceptible to bacterial wilt and RKNs, significantly reduced root galling caused by RKNs in all four field trials and increased yield in two of the trials compared with the nongrafted treatment. This study demonstrates the potential of grafting for managing multiple soilborne pathogens using the same rootstocks.

Identification of inhibitors of PvdQ, an enzyme involved in the synthesis of the siderophore pyoverdine.

Pseudomonas aeruginosa produces the peptide siderophore pyoverdine, which is used to acquire essential Fe(3+) ions from the environment. PvdQ, an Ntn hydrolase, is required for the biosynthesis of pyoverdine. PvdQ knockout strains are not infectious in model systems, suggesting that disruption of siderophore production via PvdQ inhibition could be exploited as a target for novel antibacterial agents, by preventing cells from acquiring iron in the low iron environments of most biological settings. We have previously described a high-throughput screen to identify inhibitors of PvdQ that identified inhibitors with IC50 values of ∼100 µM. Here, we describe the discovery of ML318, a biaryl nitrile inhibitor of PvdQ acylase. ML318 inhibits PvdQ in vitro (IC50 = 20 nM) by binding in the acyl-binding site, as confirmed by the X-ray crystal structure of PvdQ bound to ML318. Additionally, the PvdQ inhibitor is active in a whole cell assay, preventing pyoverdine production and limiting the growth of P. aeruginosa under iron-limiting conditions.