Assessment of the pathogen genomics landscape highlights disparities and challenges for effective AMR Surveillance and outbreak response in the East African community.

The East African Community (EAC) grapples with many challenges in tackling infectious disease threats and antimicrobial resistance (AMR), underscoring the importance of regional and robust pathogen genomics capacities. However, a significant disparity exists among EAC Partner States in harnessing bacterial pathogen sequencing and data analysis capabilities for effective AMR surveillance and outbreak response. This study assesses the current landscape and challenges associated with pathogen next-generation sequencing (NGS) within EAC, explicitly focusing on World Health Organization (WHO) AMR-priority pathogens. The assessment adopts a comprehensive approach, integrating a questionnaire-based survey amongst National Public Health Laboratories (NPHLs) with an analysis of publicly available metadata on bacterial pathogens isolated in the EAC countries. In addition to the heavy reliance on third-party organizations for bacterial NGS, the findings reveal a significant disparity among EAC member States in leveraging bacterial pathogen sequencing and data analysis. Approximately 97% (n = 4,462) of publicly available high-quality bacterial genome assemblies of samples collected in the EAC were processed and analyzed by external organizations, mainly in Europe and North America. Tanzania led in-country sequencing efforts, followed by Kenya and Uganda. The other EAC countries had no publicly available samples or had all their samples sequenced and analyzed outside the region. Insufficient local NGS sequencing facilities, limited bioinformatics expertise, lack of adequate computing resources, and inadequate data-sharing mechanisms are among the most pressing challenges that hinder the EAC's NPHLs from effectively leveraging pathogen genomics data. These insights emphasized the need to strengthen microbial pathogen sequencing and data analysis capabilities within the EAC to empower these laboratories to conduct pathogen sequencing and data analysis independently. Substantial investments in equipment, technology, and capacity-building initiatives are crucial for supporting regional preparedness against infectious disease outbreaks and mitigating the impact of AMR burden. In addition, collaborative efforts should be developed to narrow the gap, remedy regional imbalances, and harmonize NGS data standards. Supporting regional collaboration, strengthening in-country genomics capabilities, and investing in long-term training programs will ultimately improve pathogen data generation and foster a robust NGS-driven AMR surveillance and outbreak response in the EAC, thereby supporting global health initiatives.

Early warning indicators for river nutrient and sediment loads in tropical seagrass beds: a benchmark from a near-pristine archipelago in Indonesia.

In remote, tropical areas human influences increase, potentially threatening pristine seagrass systems. We aim (i) to provide a bench-mark for a near-pristine seagrass system in an archipelago in East Kalimantan, by quantifying a large spectrum of abiotic and biotic properties in seagrass meadows and (ii) to identify early warning indicators for river sediment and nutrient loading, by comparing the seagrass meadow properties over a gradient with varying river influence. Abiotic properties of water column, pore water and sediment were less suitable indicators for increased sediment and nutrient loading than seagrass properties. Seagrass meadows strongly responded to higher sediment and nutrient loads and proximity to the coast by decreasing seagrass cover, standing stock, number of seagrass species, changing species composition and shifts in tissue contents. Our study confirms that nutrient loads are more important than water nutrient concentrations. We identify seagrass system variables that are suitable indicators for sediment and nutrient loading, also in rapid survey scenarios with once-only measurements.

Green tea improves metabolic biomarkers, not weight or body composition: a pilot study in overweight breast cancer survivors.

BACKGROUND: Overweight status after breast cancer treatment may increase a woman's risk for recurrent disease and/or early onset cardiovascular disease. Green tea has been proposed to promote weight loss and favourably modify glucose, insulin and blood lipids. This pilot study tested the effect of daily decaffeinated green tea consumption for 6 months on weight and body composition, select metabolic parameters and lipid profiles in overweight breast cancer survivors. METHODS: The effect of daily decaffeinated green tea intake on weight, body composition and changes in resting metabolic rate, energy intake, glucose, insulin, homeostasis model assessment--insulin resistance (HOMA-IR) and lipids was evaluated in overweight breast cancer survivors. Participants had a mean weight of 80.2 kg; body mass index (BMI) 30.1 kg m⁻²; and body fat 46.4%. Participants (n = 54) were randomised to 960 mL of decaffeinated green or placebo tea daily for 6 months. RESULTS: Mean (SD) tea intake among study completers (n = 39) was 5952 (1176) mL week⁻¹ and was associated with a significant reduction in energy intake (P = 0.02). Change in body weight of -1.2 kg (green tea) versus +0.2 kg (placebo) suggests a weight change effect, although this was not statistically significant. Decaffeinated green tea intake was associated with elevated high-density lipoprotein (HDL) levels (P = 0.003) and nonsignificant improvements in the HDL/LDL ratio and HOMA-IR (-1.1 ± 5.9: green tea; +3.2 ± 7.2: herbal). CONCLUSIONS: Intake of decaffeinated green tea for 6 months was associated with a slight reduction in body weight and improved HDL and glucose homeostasis in overweight breast cancer survivors.

Congenital fusion of the maxilla and mandible (congenital bony syngnathia).

A rare case of syngnathia (maxillomandibular fusion) is described in a 2-year-old boy who presented from a rural area of Saudi Arabia. The child had the problem since birth and had undergone two surgical attempts to release the fusion at another institution but both had failed and recurrence occurred. In the authors' institute, the patient underwent two separate surgical procedures at the age of 2 and 3 years. Both procedures were followed by a period of aggressive physiotherapy, but the patient presented with re-fusion of the mandible and the maxilla 1 year after the first operation and 5 months after the second operation. It was decided to defer treatment until puberty. The cause of the relapse may be the high osteogenic potential because of his youth or the failure of the parents to maintain the active physiotherapy protocol because they live in a rural area and close follow-up was difficult. A possible genetic predisposition for bone formation at this site should be investigated.

Evaluation of distracted mandibular bone using computed tomography scan and ultrasonography: technical note.

OBJECTIVES: Distraction osteogenesis is considered an important reconstruction armamentarium in the management of mandibular deformities and deficiency disorders. The duration of the consolidation period is still a debatable issue among the clinicians. Evaluation of the newly formed bone is the cornerstone for terminating the consolidation period safely. The aim of this study is to find a more conservative protocol for the evaluation of callus distraction by monitoring bone healing using two different examination tools: ultrasonography and dental CT. METHODS: Four adult patients (three women and one man) underwent mandibular distraction (using two intraoral and two extraoral devices). The latency period was 5-7 days and the distraction was at a rate of 2 mm per day, with 12-14 weeks of consolidation. All patients were evaluated during activation, 3 months, 6 months and 1 year post-distraction. Evaluation included clinical examination, plain radiographs, CT and ultrasonography examinations. RESULTS: Ultrasonographic examination of the healing callus revealed four different phases of maturation. These phases were similar to the degree of tissue calcification as measured by CT. Tissue density across the distraction wound at the time of distractor removal (12-14 weeks) was equal to or less than one-third of normal bone density. CONCLUSIONS: Clinical monitoring of mandibular distraction wounds can be successfully achieved through frequent use of ultrasonographic examinations. Standardization of ultrasonography based on CT findings will expand the reliability of ultrasound in monitoring callus maturation. An algorithm for evaluation of distraction wound healing is suggested.

Alternative surgical approaches for excision of dermoid cyst of the floor of mouth.

Two different treatment approaches for large dermoid cysts are presented in this article. The extraoral approach was utilized for a patient who presented to the emergency room with a respiratory problem. The intraoral approach was performed in a female patient presenting with a large swelling involving both the submental and sublingual areas, and this approach led to good esthetic results without recurrence.

Tempromandibular joint (TMJ) response to intra-articular dexamethasone injection following mechanical arthropathy: a histological study in rats.

The purpose of this study was to evaluate as well as to compare the effect of intra-articular versus intra-peritoneal injection of dexamethasone on synovitis induced by trauma to the rat's TMJ. Twenty-seven male Wister rats were included in the present study. Induced forced condylar hypermobility achieved through opening the rat's mouth manually 10 times for 10 consecutive days. Rats were randomized into three groups (3 rats in the control group, and 24 rats in both experimental groups). Group I (control group): Rats of this group were left without any treatment after induction of synovitis. Group II: Rats were injected with a single dose of 1.2 mg/kg dexamethasone intra-articularly (after 10 days). Group III: Rats were injected with a single intra-peritoneal injection of 1.2 mg/kg dexamethasone (after 10 days). Control rats were sacrificed at 6 weeks, while rats in Groups II and III were sacrificed at 1 and 6 weeks after drug injection, then joints were dissected and processed for histological study. The condylar head of the rats injected with intra-articular dexamethasone showed resorption with active osteoclastic activity, although the drug was given only once. This might be an alarming sign of the severe adverse effect(s) of the local injection of dexamethasone.

Preliminary investigation into the effects of electrical stimulation on mandibular distraction osteogenesis in goats.

Craniofacial distraction osteogenesis (DO) was found to be a procedure with low preoperative and postoperative morbidity. Direct current electrical stimulation is used clinically to treat different orthopaedic problems. It provided a significant increase in new-bone formation, and a higher mechanical strength of healing. The purpose of this study was to test the effect of electric current on distraction osteogenesis and to establish the best period to apply an electric current during the different distraction phases. Twelve healthy adult goats were subjected to a vertical osteotomy in the symphyseal area. A distraction device was fixed to the bone. Animals were divided into two groups, Group I (three goats) and group II (nine goats). In group I, the device was activated 1mm per day for 10 days; while in group II, the device was activated 1mm per day for 10 days with the application of direct electric current stimulation of 10 microA either during the first 3 days of latency in a continuous mode (ESL group), or during the first 3 days of the activation period in a continuous mode (ESA group); or during the first 3 days of the consolidation period in a continuous mode (ESC group). After the activation period was completed, the distraction device left in place for additional 15 days for bone consolidation in all animals. Animals were then sacrificed, the mandible was harvested, and the distracted areas were removed and processed for mechanical and histological studies. The results of this study suggested that direct current electrical stimulation display synergism on mandibular distraction when this stimulation applied to the distraction zone during activation or consolidation periods.

Habitual tea consumption and risk of osteoporosis: a prospective study in the women's health initiative observational cohort.

The purpose of this study was to prospectively investigate associations of habitual drinking of regular tea with bone mineral density and fracture risk. Study participants were a multiethnic postmenopausal cohort (n = 91,465) from the nationwide Women's Health Initiative Observational Study. These women were recruited in the United States and aged 50-79 years at the time of enrollment (1994-1998). The average follow-up time was 4.1 years. Habitual consumption of regular tea was assessed with a structured questionnaire at baseline. Clinical fractures during the follow-up were reported in questionnaires, and hip fractures were further confirmed by reviewing medical records. Bone mineral density measurements were conducted among a subgroup of women (n = 4,979) at three Women's Health Initiative bone mineral density centers using dual-energy x-ray absorptiometry. Multivariate analyses suggested a positive trend of increased total body bone mineral density with tea drinking (p < 0.05). However, results from the Cox proportional hazard models did not show any significant association between tea drinking and the risk of fractures at the hip and forearm/wrist. In conclusion, the results from this study indicate that the effect of habitual tea drinking on bone density is small and does not significantly alter the risk of fractures among the US postmenopausal population.

Atypical fibroxanthoma.

This is the first case report of atypical fibroxanthoma in the otolaryngology literature. Atypical fibroxanthoma is a rare fibrohistiocytic tumor that occurs on actinically damaged skin. The typical presentation is a nodular lesion in sun-exposed areas of the head and neck in an elderly patient. Differentiating atypical fibroxanthoma from other soft tissue sarcomas, such as dermatofibrosarcoma protuberans and malignant fibrous histiocytoma, can be difficult. Treatment should be wide local excision with a 1-cm margin. In cosmetically important regions in which tissue preservation is important, Mohs' surgery should be considered.

Tumor necrosis factor-alpha mediates RANK ligand stimulation of osteoclast differentiation by an autocrine mechanism.

Osteoblasts or bone marrow stromal cells are required as supporting cells for the in vitro differentiation of osteoclasts from their progenitor cells. Soluble receptor activator of nuclear factor-kappaB ligand (RANKL) in the presence of macrophage colony-stimulating factor (M-CSF) is capable of replacing the supporting cells in promoting osteoclastogenesis. In the present study, using Balb/c-derived cultures, osteoclast formation in both systems-osteoblast/bone-marrow cell co-cultures and in RANKL-induced osteoclastogenesis-was inhibited by antibody to tumor necrosis factor-alpha (TNF-alpha), and was enhanced by the addition of this cytokine. TNF-alpha itself promoted osteoclastogenesis in the presence of M-CSF. However, even at high concentrations of TNF-alpha the efficiency of this activity was much lower than the osteoclastogenic activity of RANKL. RANKL increased the level of TNF-alpha mRNA and induced TNF-alpha release from osteoclast progenitors. Furthermore, antibody to p55 TNF-alpha receptors (TNF receptors-1) (but not to p75 TNF-alpha receptors (TNF receptors-2) inhibited effectively RANKL- (and TNF-alpha() induced osteoclastogenesis. Anti-TNF receptors-1 antibody failed to inhibit osteoclastogenesis in C57BL/6-derived cultures. Taken together, our data support the hypothesis that in Balb/c, but not in C57BL/6 (strains known to differ in inflammatory responses and cytokine modulation), TNF-alpha is an autocrine factor in osteoclasts, promoting their differentiation, and mediates, at least in part, RANKL's induction of osteoclastogenesis.

Joint effects of citrus peel use and black tea intake on the risk of squamous cell carcinoma of the skin.

BACKGROUND: Differences in tea drinking habits and/or citrus peel use are likely to vary by populations and could contribute to the inconsistencies found between studies comparing their consumption and cancer risk. METHODS: A population-based case-control study was used to evaluate the relationships between citrus peel use and black tea intake and squamous cell carcinoma (SCC) of the skin. Moreover, we assessed the independent and interactive effects of citrus peel and black tea in the development of SCC. RESULTS: Hot and iced teas were consumed by 30.7% and 51.8% of the subjects, respectively. Peel consumption was reported by 34.5% of subjects. Controls were more likely than were cases to report citrus peel use (odds ratio (OR) = 0.67) and hot tea intake (OR = 0.79). After adjustment for hot and iced tea intake, the ORs associated with citrus peel use were 0.55 and 0.69, respectively, whereas the corresponding adjusted ORs for hot and iced tea intake after adjustment for citrus peel use were 0.87 and 1.22 respectively. Compared with those who did not consume hot black tea or citrus peel, the adjusted ORs associated with sole consumption of hot black tea or citrus peel were 0.60 and 0.30, respectively. Subjects who reported consumption of both hot black tea and citrus peel had a significant marked decrease (OR= 0.22; 95% CI = 0.10 - 0.51) risk of skin SCC. CONCLUSION: These results indicate that both citrus peel use and strong (hot) black tea have independent potential protective effects in relation to skin SCC.

Reproducibility and relative validity of a questionnaire to assess intake of black tea polyphenols in epidemiological studies.

Epidemiological studies suggest that tea drinking may reduce the risk of cardiovascular diseases and cancers. Although tea is an important source of antioxidant phytochemicals, variation in preparation techniques may translate to variation in antioxidant capacity. However, most large-scale epidemiological studies use regular food frequency questionnaires to estimate tea intake, and nationally available nutrient analysis databases do not include levels of black tea polyphenols. The Arizona Tea Questionnaire (ATQ) was designed as a tool for collecting more complete dietary tea consumption information, and a database was developed after analyzing 40 black tea samples (brewed, instant, and sun tea) for polyphenols. This study assesses the reliability and relative validity of the ATQ and polyphenol database. Relative validity of estimates of black tea consumption was tested by comparing the ATQ with the traditional Arizona Food Frequency Questionnaire and four days of food records. The ATQ was tested for reproducibility of estimates of black (hot and iced) tea consumption and levels of black tea polyphenol intake. Correlations between two measures of intake taken 2 months apart ranged from 0.72 for black hot tea to 0.86 for black sun tea. Mean intakes (range) of total flavonoids for black tea consumers were 80.8 (3.0-588.0) mg/day at the first ATQ and 102.4 (4.5-802.3) mg/day at the second ATQ (r = 0.83, P < 0.001). The ATQ provided highly reproducible estimates of both total tea consumption and individual tea polyphenol intake. This instrument may be a useful tool in studies of the associations between tea consumption, tea polyphenols intake, and risk for chronic disease.

Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E.

Green tea has been shown to exhibit cancer-preventive activities in preclinical studies. Its principal active components include epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin (EC), and epicatechin gallate, of which EGCG is the most abundant and possesses the most potent antioxidative activity. We performed a Phase I pharmacokinetic study to determine the systemic availability of green tea catechins after single oral dose administration of EGCG and Polyphenon E (decaffeinated green tea catechin mixture). Twenty healthy subjects (five subjects/dose level) were randomly assigned to one of the dose levels (200, 400, 600, and 800 mg based on EGCG content). All subjects were randomly crossed-over to receive the two catechin formulations at the same dose level. Blood and urine samples were collected for up to 24 h after oral administration of the study medication. Tea catechin concentrations in plasma and urine samples were determined using high-performance liquid chromatography with the coulometric electrode array detection system. After EGCG versus Polyphenon E administration, the mean area under the plasma concentration-time curves (AUC) of unchanged EGCG were 22.5 versus 21.9, 35.4 versus 52.2, 101.9 versus 79.7, and 167.1 versus 161.4 min x microg/ml at the 200-, 400-, 600-, and 800-mg dose levels, respectively. EGC and EC were not detected in plasma after EGCG administration and were present at low/undetectable levels after Polyphenon E administration. High concentrations of EGC and EC glucuronide/sulfate conjugates were found in plasma and urine samples after Polyphenon E administration. There were no significant differences in the pharmacokinetic characteristics of EGCG between the two study medications. The AUC and maximum plasma concentration (Cmax) of EGCG after the 800-mg dose of EGCG were found to be significantly higher than those after the 200- and 400-mg dose. The AUC and Cmax of EGCG after the 800-mg dose of Polyphenon E were significantly higher than those after the three lower doses. We conclude that the two catechin formulations resulted in similar plasma EGCG levels. EGC and EC were present in the body after the Polyphenon E administration; however, they were present predominantly in conjugated forms. The systemic availability of EGCG increased at higher doses, possibly due to saturable presystemic elimination of orally administered green tea polyphenols.

Enhanced major histocompatibility complex class I-dependent presentation of antigens modified with cationic and fusogenic peptides.

Soluble extracellular protein antigens are notoriously poor stimulators of CD8+ cytotoxic T-lymphocyte (CTL) responses, largely because these antigens have inefficient access to an endogenous cytosolic pathway of the major histocompatibility complex (MHC) class I-dependent antigen presentation. Here, we present a strategy that facilitates antigen penetration into the cytosol of antigen-presenting cells (APC) by addition to the antigen of charge-modifying peptide sequences. As a result of this intervention, the charge modification enhances antigen uptake into APC by counteracting the repulsive cell surface charge, and then endosomal membranes are disrupted with a subsequent release of antigen into the cytosol. This technology significantly improves MHC class I-dependent antigen presentation to CTL, enabling a more efficient generation of specific CTL immunity in vivo. The strategy described here has potential for use in developing efficient vaccines for antigen-specific immunotherapy of human malignancies.

Tea intake and squamous cell carcinoma of the skin: influence of type of tea beverages.

Differences in tea drinking habits are likely to vary by populations and could contribute to the inconsistencies found between studies comparing tea consumption and cancer risk. A population-based case-control study was used to evaluate how usual tea consumption patterns of an older population (n = 450) varied with history of squamous cell carcinoma (SCC) of the skin. A detailed tea questionnaire was developed to assess specific tea preparation methods and patterns of drinking. In this southwestern United States population, black tea was the predominant variety of tea consumed. We found no association between the broad definition of any tea consumption and skin SCC. However, the adjusted odds ratios (ORs) for hot and iced black tea intake were 0.63 [95% confidence interval (CI), 0.36-1.10] and 1.02 (95% CI, 0.64-1.63), respectively. Controls were more likely to report usually drinking strong hot tea (OR, 0.74; 95% CI, 0.53-1.03) with increased brewing time (P for trend = 0.03). Adjusting for brewing time, the association between skin SCC and hot black tea consumption suggests a significantly lower risk in consumers of hot tea compared to nonconsumers (OR, 0.33; 95% CI, 0.12-0.87). This is one of the first studies to explore the relation between different types of tea consumption and occurrence of human cancers. Our results show that tea concentration (strength), brewing time, and beverage temperature have major influences on the potential protective effects of hot black tea in relation to skin SCC. Further studies with increased sample sizes are needed to evaluate the interrelationships between preparation techniques, tea type, and other life-style factors.

Fat intake and risk of squamous cell carcinoma of the skin.

The varied effects of different classes of dietary fatty acids on carcinogenesis suggest that fatty acid composition is an important determining factor in tumor development. In the present study, we investigated the association between dietary n-3 and n-6 fatty acid intake and risk of squamous cell carcinoma of the skin (SCC). Data were taken from a population-based case-control study of skin SCC in Southeastern Arizona. Our data show a consistent tendency for a lower risk of SCC with higher intakes of n-3 fatty acids [p (for trend) = 0.055]. The adjusted odds ratios for increasing levels of n-3 fatty acids were 0.85 [95% confidence interval (CI) = 0.56-1.27] and 0.71 (95% CI = 0.49-1.00) compared with the lower level as the referent. For the ratio of n-3 to n-6 fatty acids, the odds ratios in successively higher levels were 0.88 (95% CI = 0.59-1.32) and 0.74 (95% CI = 0.51-1.05), suggesting a tendency toward decreased risk of SCC with increased intake of diets with high ratio of n-3 to n-6 fatty acid. More studies are clearly needed to elucidate the function of dietary fatty acids so that recommendations can be made to alter the human diet for cancer prevention, particularly in light of the increasing incidence of SCC of the skin.

Citrus peel use is associated with reduced risk of squamous cell carcinoma of the skin.

Limonene has demonstrated efficacy in preclinical models of breast and colon cancers. The principal sources of d-limonene are the oils of orange, grapefruit, and lemon. The present case-control study was designed to determine the usual citrus consumption patterns of an older Southwestern population and to then evaluate how this citrus consumption varied with history of squamous cell carcinoma (SCC) of the skin. In this Arizona population, 64.3% and 74.5% of the respondents reported weekly consumption of citrus fruits and citrus juices, respectively. Orange juice (78.5%), orange (74.3%), and grapefruit (65.3%) were the predominant varieties of citrus consumed. Peel consumption was not uncommon, with 34.7% of all subjects reporting citrus peel use. We found no association between the overall consumption of citrus fruits [odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.73-1.32] or citrus juices (OR = 0.97, 95% CI = 0.71-1.31) and skin SCC. However, the most striking feature was the protection purported by citrus peel consumption (OR = 0.66, 95% CI = 0.45-0.95). Moreover, there was a dose-response relationship between higher citrus peel in the diet and degree of risk lowering. This is the first study to explore the relationship between citrus peel consumption and human cancers. Our results show that peel consumption, the major source of dietary d-limonene, is not uncommon and may have a potential protective effect in relation to skin SCC. Further studies with large sample sizes are needed to more completely evaluate the interrelationships between peel intake, bioavailability of d-limonene, and other lifestyle factors.

The effect of fibrin stabilizing factor (F.XIII) on healing of bone defects in normal and uncontrolled diabetic rats.

This study was undertaken to examine the effect of fibrin stabilizing factor (F.XIII) on healing of bone defects in normal and uncontrolled diabetic rats. Eighty rats were divided into two groups: group I (diabetic) and group II (non-diabetic) (40 rats each). Diabetes was induced in group I using streptozotocin. Both groups were divided into two subgroups, control and experimental (20 rats each). Bone defect was created in the mandible. Rats in the experimental subgroups were injected with F.XIII, while those of the control groups were injected with saline (F.XIII solvent). Animals were killed at varying intervals and tissue sections stained with hematoxyline and eosin and Van-Gieson stains were examined. Differences in collagen deposition and bone formation were compared in both control and experimental groups. Collagen deposition was evident and appeared more oriented in diabetic rats treated with F.XIII, and signs of bone deposition started in the experimental group earlier than in the control group. On the other hand, F.XIII did not significantly affect healing in non-diabetic rats. It is concluded from these results that F.XIII may enhance early stages of bone healing in uncontrolled diabetic rats.