A geospatial platform to support visualization, analysis, and prediction of tuberculosis notification in space and time.

Background: Tuberculosis has caused significant public health and economic burdens in Vietnam over the years. The Vietnam National Tuberculosis Program is facing considerable challenges in its goal to eliminate tuberculosis by 2030, with the COVID-19 pandemic having negatively impacted routine tuberculosis services at all administrative levels. While the turnaround time of tuberculosis infection may delay disease detection, high transportation frequency could potentially mislead epidemiological studies. This study was conducted to develop an online geospatial platform to support healthcare workers in performing data visualization and promoting the active case surveillance in community as well as predicting the TB incidence in space and time. Method: This geospatial platform was developed using tuberculosis notification data managed by The Vietnam National Tuberculosis Program. The platform allows case distribution to be visualized by administrative level and time. Users can retrieve epidemiological measurements from the platform, which are calculated and visualized both temporally and spatially. The prediction model was developed to predict the TB incidence in space and time. Results: An online geospatial platform was developed, which presented the prediction model providing estimates of case detection. There were 400,370 TB cases with bacterial evidence to be included in the study. We estimated that the prevalence of TB in Vietnam was at 414.67 cases per 100.000 population. Ha Noi, Da Nang, and Ho Chi Minh City were predicted as three likely epidemiological hotspots in the near future. Conclusion: Our findings indicate that increased efforts should be undertaken to control tuberculosis transmission in these hotspots.

COMOKIT: A Modeling Kit to Understand, Analyze, and Compare the Impacts of Mitigation Policies Against the COVID-19 Epidemic at the Scale of a City.

Since its emergence in China, the COVID-19 pandemic has spread rapidly around the world. Faced with this unknown disease, public health authorities were forced to experiment, in a short period of time, with various combinations of interventions at different scales. However, as the pandemic progresses, there is an urgent need for tools and methodologies to quickly analyze the effectiveness of responses against COVID-19 in different communities and contexts. In this perspective, computer modeling appears to be an invaluable lever as it allows for the in silico exploration of a range of intervention strategies prior to the potential field implementation phase. More specifically, we argue that, in order to take into account important dimensions of policy actions, such as the heterogeneity of the individual response or the spatial aspect of containment strategies, the branch of computer modeling known as agent-based modeling is of immense interest. We present in this paper an agent-based modeling framework called COVID-19 Modeling Kit (COMOKIT), designed to be generic, scalable and thus portable in a variety of social and geographical contexts. COMOKIT combines models of person-to-person and environmental transmission, a model of individual epidemiological status evolution, an agenda-based 1-h time step model of human mobility, and an intervention model. It is designed to be modular and flexible enough to allow modelers and users to represent different strategies and study their impacts in multiple social, epidemiological or economic scenarios. Several large-scale experiments are analyzed in this paper and allow us to show the potentialities of COMOKIT in terms of analysis and comparison of the impacts of public health policies in a realistic case study.

Actin Disruption Results in Altered Morphology of Basal Tubulobulbar Complexes in Rat Seminiferous Epithelium.

Basal tubulobulbar complexes (TBCs) that occur at attachment sites between neighboring Sertoli cells are subcellular machines that internalize intercellular junctions during movement of spermatocytes from basal to adluminal compartments of the seminiferous epithelium. Each complex consists of an elongate tubular extension of two attached plasma membranes, and is capped at its distal end by a clathrin-coated pit. The tubular region is surrounded by a cuff of actin arranged in a dendritic network. Near the end of the complex, a bulbous region forms that lacks the actin cuff but is closely associated with cisternae of endoplasmic reticulum. The bulb eventually buds from the complex and enters endocytic compartments of the Sertoli cell. Previous research has shown that when the actin network is perturbed using the actin filament-disruptor, cytochalasin D, apical tubulobulbar complexes that are associated with spermatids were associated with lower levels of actin, patchy actin networks and swollen tubular regions. Here we explored the effects of actin network perturbation on the morphology of basal tubulobulbar complexes in stage V seminiferous tubules. Isolated rat testes were perfused ex vivo for one hour with oxygenated Krebs-Henseleit buffer (with BSA) containing either 40 µM cytochalasin D or control solution containing DMSO and perfusion-fixed for electron microscopy. Compared to control, actin cuffs in drug-treated TBCs appeared less uniform and patchy. In addition, the tubular regions of the complexes appeared swollen. Our results are consistent with the conclusion that intact networks of actin filaments are required for maintaining the structural integrity of basal TBCs. Anat Rec, 299:1449-1455, 2016. © 2016 Wiley Periodicals, Inc.

Topical therapy with imiquimod for eyelid lesion.

Herein a case of clinically diagnosed lower eyelid lesion treated with topical imiquimod is reported. Macroscopic resolution of the lesion occurred 4 weeks after treatment with good cosmetic result. This is the first reported successful case of using this drug in treating eyelid lesion involving the lid margin.

The Australian Mohs database: periocular squamous intraepidermal carcinoma.

OBJECTIVE: To present the findings and report the outcomes of all patients with periocular squamous intraepidermal carcinoma (IEC) treated with Mohs micrographic surgery (MMS) in Australia between 1993 and 1999. DESIGN: Prospective, noncomparative, multicenter, interventional case series. METHODS: A prospective series of 53 patients undergoing MMS for periocular IEC over a 7-year period (1993-1999). MAIN OUTCOME MEASURES: Recurrence, site, size of IEC, prior recurrence, and size of final defect. RESULTS: Fifty-three patients had 27 (51%) lower eyelid, 17 (32%) medial canthus, and 9 (17%) upper eyelid IEC. Most (85%) of the IECs were present for less than 5 years. Fifty-eight percent were primary IECs, and 42% were recurrent IECs. There were no differences in the clinical features of primary and recurrent IECs. Significant subclinical tumor extension was found, whereby the defect exceeded tumor size by at least 2 size groups (> or =2 cm) in 25% of cases. Follow-up to date was available in 68% (36 of 53) of cases (19 primary and 17 recurrent IECs). With a mean follow-up of 77.4 months (median, 75; range, 44-120 months), 3 (8.3%; exact 95% confidence interval 1.8%-23.1%) cases recurred. Hence, the recurrence rate was 5.3% (1 of 19) for primary periocular IEC and 11.8% (2 of 17) for recurrent periocular IEC. CONCLUSIONS: The Australian MMS database provides data for the first prospective series of periocular IEC managed by MMS. Periocular IEC demonstrates significant subclinical tumor extension, with no significant differences in the clinical features of primary and recurrent lesions. Compared with other published studies, the recurrence rate of 5% and 12% for primary and recurrent lesions, respectively, with more than 5-years of follow-up for most cases emphasizes the importance of margin-controlled excision for periocular IEC.

The Australian Mohs database: periocular squamous cell carcinoma.

OBJECTIVE: To present the results of all patients with periocular squamous cell carcinoma (SCC) treated with Mohs' micrographic surgery (MMS) in Australia between 1993 and 1999. DESIGN: Prospective, noncomparative, multicenter, interventional case series. PARTICIPANTS: Seventy-nine patients undergoing MMS for periocular SCC over a 7-year period (1993-1999). MAIN OUTCOME MEASURES: Recurrence after MMS, site, size, prior recurrence, defect size, histologic subtype, and presence of perineural invasion (PNI). RESULTS: Seventy-nine patients had 54 (68%) lower eyelid, 19 (24%) medial canthus, and 6 (7.6%) upper eyelid SCCs. The most common histologic subtypes were well differentiated (48.7%) and moderately differentiated (35.1%) SCC. Seventy-three percent were primary tumors and 27% were recurrent tumors. Three (4.3%) cases had histologically confirmed PNI. Two of the 3 cases with PNI were recurrent (P = 0.1355), and surgical excision was the most frequent prior treatment (P = 0.0192), with up to 3 prior excisions in 1 case. None of the patients with PNI received adjunctive radiotherapy, and none have recurred with follow-ups to date of 4, 5, and 6 years, respectively. A median follow-up of 73 months (mean, 77.3; range, 42-117) was available in 56 (71%) cases, of which 2 (3.64%; exact 95% confidence interval, 0.44%-12.53%) recurred. Both cases were primary, moderately differentiated SCCs. CONCLUSION: This is the largest reported prospective series of periocular SCC managed by MMS, with a median follow-up of over 5 years. It demonstrates that MMS has the lowest reported recurrence rate (3.64%) of any treatment modality for periocular SCC. That there were no recurrences for cases with PNI further emphasizes the importance of margin-controlled excision for periocular SCC.

The Australian Mohs database, part I: periocular basal cell carcinoma experience over 7 years.

OBJECTIVE: To present the findings of all patients with periocular basal cell carcinoma (BCC) treated with Mohs' micrographic surgery (MMS) in Australia between 1993 and 1999. DESIGN: Prospective, noncomparative, multicenter, interventional case series. METHODS: Prospective series of 1295 patients undergoing MMS for periocular BCC over a 7-year period (1993-1999). INCLUSION CRITERIA: Periocular BCC referred for MMS. MAIN OUTCOME MEASURES: Site, tumor size, prior occurrence, defect size, histologic subtype, and presence of perineural invasion. RESULTS: Twelve hundred ninety-five patients had 615 (47.5%) lower eyelid, 626 (48.3%) medial canthus, and 51 (3.9%) upper eyelid BCCs. The most common histologic subtypes were nodulocystic (39.5%) and infiltrating (34.8%) (P = 0.0008). Sixty-eight percent were primary and 32% were recurrent tumors. Previously recurrent BCCs were larger (P<0.0001), with larger defects (P<0.0001) than primary BCCs, and had more subclinical extension (P<0.0001) requiring more levels for complete excision (P<0.0001). Furthermore, superficial BCCs were more likely to have a prior occurrence (P<0.0001). In this series, perineural invasion was found in 1% of cases, with greater subclinical tumor extension in such cases (P = 0.0657). CONCLUSION: The Australian MMS database is the largest prospective, nationwide series of high-risk periocular BCC managed by MMS. Almost 50% of tumors were at the medial canthus, with nodulocystic and infiltrating being the most common histologic subtypes. Recurrent BCCs comprised a third of tumors and were larger, with larger defects and more subclinical extension than primary BCCs. Perineural invasion was found in 1% of cases and also had greater subclinical extension.

The Australian Mohs database, part II: periocular basal cell carcinoma outcome at 5-year follow-up.

OBJECTIVE: To report the outcome with 5-year strict follow-up (only cases where 5-year follow-up is available) of all patients with periocular basal cell carcinoma (BCC) treated with Mohs' micrographic surgery (MMS) in Australia between 1993 and 1996. DESIGN: Prospective, noncomparative, multicenter, interventional case series. METHODS: A prospective series of 819 patients, undergoing MMS for periocular BCC over a 3-year period (1993-1996). INCLUSION CRITERIA: Periocular BCC referred for MMS. MAIN OUTCOME MEASURES: Recurrence, site, size, prior occurrence, defect size, histologic subtype, and presence of perineural invasion. RESULTS: Eight hundred nineteen patients had 257 (54%) lower eyelid, 195 (41%) medial canthus, and 22 (5%) upper eyelid BCCs. The most common histologic subtypes were nodulocystic (43%) and infiltrating (30%) (P = 0.0003). Sixty-eight percent were primary and 32% were recurrent tumors. Five-year follow-ups for cases between 1993 and 1996 were available in 347 (42%) cases. There were 7 recurrences (2.0%; exact 95% confidence interval [CI]: 0.82%-4.1%), 5 of which were at the medial canthus and all of which were previously recurrent, with up to 3 recurrences before MMS. Previous recurrence (P<0.0001), infiltrating (5) or superficial (2) histologic subtype (P = 0.0882), and medial canthal site were the main predictors of recurrence after MMS. There were no recurrences for primary BCC, and the 5-year recurrence for previously recurrent BCC was 7.8% (exact 95% CI: 3.2%-15.4%). CONCLUSION: The Australian MMS database is the largest prospective nationwide series of periocular BCC managed by MMS. The strict 5-year recurrence rates of 0% and 7.8% for primary and recurrent tumors, respectively, confirm MMS as the treatment of choice for periocular BCC.

Transmembrane T-cell receptor peptides inhibit B- and natural killer-cell function.

A synthetic hydrophobic peptide (core peptide; CP) containing two positively charged amino acids, lysine and arginine was derived from the transmembrane sequence of the T-cell receptor (TCR) alpha chain and has been shown to inhibit T-cell-mediated inflammation. In this study, we investigated the specificity of CP (10 microm) on lymphocyte function and found that it significantly inhibited interleukin-2 production in T cells and natural killer cytotoxicity by 46-58% compared to positive control. CP had no effects on B-cell proliferative responses when used at these concentrations; however, it suppressed B-cell proliferation at higher concentrations (50 microm). Inhibition by CP was not the result of membrane pore formation or cytotoxicity when examined by trypan blue, propidium iodide staining or transmission electron microscopy. CP analogues, with both lysine and arginine replaced by neutral or negatively charged amino acids, or by randomly distributing charges in the peptide sequence, had no effect on lymphocyte function. These results suggest that peptide inhibition is affected by its structure and charge interactions, and may involve common signalling molecules in T, B and natural killer cells. The potential of the immuno-inhibitory effects of CP as a novel anti-inflammatory peptide in therapy should be further explored.

Survey of phototherapy practice by dermatologists in Australia.

A postal survey was sent to all dermatologists in Australia to determine current phototherapy practices. Questionnaires were returned by 158 (57%) of 277 dermatologists, of whom 112 (71%) provided phototherapy. Large variations existed in attitudes and practice, including indications, contraindications, dosage schedules, equipment maintenance, response to adverse events, and follow-up arrangements. Cumulative ultraviolet (UV) doses for psoralen and UVA (PUVA) were not calculated by 21%, while 30% did not calculate cumulative doses for UVB. Written informed consent was not obtained by 32%. Phototherapist dermatologists reported 25 patients developing melanoma following PUVA. Only 30% of Australian dermatologists organize regular follow up of patients after phototherapy. Australians have the highest rates of melanoma and non-melanoma skin cancers in the world, because of their ancestry and high solar exposure. This makes it inappropriate for Australian dermatologists to rely entirely on foreign safety data when assessing the risks and benefits of phototherapy in Australian patients. There is a need for standardized Australian guidelines that can be prospectively assessed to ensure phototherapy is used to maximize efficacy and minimize risks in Australian patients, given their unique ancestral mix and outdoor lifestyle.

Scrubbing for cutaneous procedures can be hazardous.

Office-based minor cutaneous surgery is a service provided by many medical practitioners. In New South Wales, Australia, it is a legal requirement for practitioners to surgically scrub before donning sterile gloves for all forms of invasive surgery, including minor cutaneous procedures. Frequent scrubbing causes altered skin barrier function, irritant dermatitis and a potential risk of latex sensitization. These adverse effects are associated with significant morbidity and cost. Better tolerated alternatives, including alcohol-based hand rubs, should be considered in preference to traditional surgical scrubs in order to reduce these occupational risks for minor proceduralists. Well-controlled, prospective studies should explore what extent of hand washing is necessary for donning sterile gloves for minor cutaneous surgery.

Basal cell carcinoma of the lip treated with radiotherapy.

Basal cell carcinoma (BCC) of the lip is uncommon relative to other cutaneous sites for BCC, such as the central face or scalp. A female predisposition and predilection for the upper lip have been previously documented. A retrospective analysis of patients treated for BCC of the lip was undertaken within the department of Radiation Oncology, Westmead Hospital, Sydney. Twenty patients were identified; 12 women and 8 men. The majority (15/20) had T1 lesions of the upper lip (17/20). Eleven patients were referred for radiotherapy alone and nine for adjuvant radiotherapy following either incomplete excision or local recurrence. With a mean follow up of 36 months no patient has recurred following either definitive or adjuvant radiotherapy. Despite the majority of BCCs of the lip being amenable to surgery fractionated external beam radiotherapy remains an option especially when functional and/or cosmetic concerns are an issue. We present the findings from this small case series and use our findings to illustrate the role of radiotherapy in treating BCC of the lip.

Merkel cell carcinoma and multiple cutaneous squamous cell carcinomas in a patient with pityriasis rubra pilaris.

A 79-year-old female was diagnosed with Merkel cell carcinoma (MCC) and multiple cutaneous squamous cell carcinomas (SCC) occurring on a background of pityriasis rubra pilaris. At the time of initial diagnosis and treatment for upper limb MCC, axillary nodal metastases were clinically evident. In the ensuing months, she developed multiple rapidly progressing SCC and eventually a left arm soft tissue deposit of metastatic MCC. Treatment involved multiple courses of fractionated radiotherapy. The salient clinical features and supporting evidence for this case are presented.