Complete Rupture of Testis After Blunt Trauma.

Testicular trauma can be classified aetiologically as blunt or penetrative. Bicycles and motorbikes are considered high risk for road traffic accidents accounting for 9-17% % of all blunt trauma. We present a case of assessment and management of isolated blunt testicular trauma in a tertiary care hospital. A 36-year-old gentleman presented to the accident and emergency department with testicular pain after a road traffic accident while riding a motorcycle. On arrival, he was fully conscious and denied any other injuries. On examination, he had bruising and gross swelling of the right hemiscrotum. Ultrasound of the scrotum revealed testicular rupture and emergency exploration was undertaken which confirmed the diagnosis. Testis was non-salvageable therefore orchidectomy was done. The patient had unremarkable post-operative recovery. A majority of testicular ruptures are secondary to blunt trauma mainly caused by sport-related injuries and road traffic accidents. Ultrasonography remains a non-invasive modality to investigate testicular injuries with a sensitivity of 100%. When not available in an emergency setting, scrotal exploration should be undertaken for both diagnostic and therapeutic purposes. Surgical repair done within 72 hours yields a 90% salvage rate after which the salvage rate is reduced significantly. Tumor markers should be checked in patients managed conservatively. Early assessment and diagnosis are crucial in the management of acute testicular rupture. Early intervention can salvage injured testes and an orchidectomy can be avoided.

Hepatitis C virus/Hepatitis B virus coinfection: Current prospectives.

In endemic areas, hepatitis C virus (HCV)/hepatitis B virus (HBV) coinfection is common, and patients with coinfection have a higher risk of developing liver disease such as hepatocellular carcinoma, liver fibrosis and cirrhosis. In such cases, HCV predominates, and HBV replication is suppressed by HCV. HCV core proteins and interferons that are activated by HCV are responsible for the suppression of HBV. Immunosuppression is also seen in patients with HCV and HBV coinfections. A decrease in HCV-neutralizing antibody response and circulation of Th1-like Tfh cells is observed in patients with HCV and HBV coinfection. Both viruses interacted in the liver, and treatment of HCV/HBV coinfection is genotype-based and complex due to the interaction of both viruses. In HCV-dominant cases, direct-acting antiviral drugs and peg interferon plus ribavirin are used for the treatment, with continuous monitoring of AST and ALT. HBV-dominant cases are less common and are treated with peg interferon and nucleoside nucleotide analogues with monitoring of AST and ALT. The SVR rate in HCV-HBV coinfection is higher than that in monoinfection when treated with direct-acting antiviral drugs. But there is a risk of reactivation of HBV during and after therapy. The rate of reactivation is lower in patients treated with direct-acting antiviral drugs as compared to those treated with peg interferon plus ribavirin. Biomarkers of HBV such as HBcrAg, HBV DNA and HBVpg RNA are not effective in the prediction of HBV reactivation; only the hepatitis B surface antigen titre can be used as a biomarker for HBV reactivation. HCV can also be reactive, but this is found in very rare cases in which HBV is present and is treated first.

Combinatorial Therapeutic Potential of Stem Cells and Benzimidazol Derivatives for the Reduction of Liver Fibrosis.

(1) Background: Liver fibrosis is currently one of the top ten causes of death worldwide. Stem cells transplantation using mesenchymal stem cells (MSCs) is an alternative therapy which is used in the place of organ transplant, due to the incapacity of stem cells to endure oxidative stress in the damage site, thus affecting the healing process. The present study aimed to enhance the therapeutic potential of MSCs using combined therapy, along with the novel synthetic compounds of benzimidazol derivatives. (2) Methods: Eighteen compound series (benzimidazol derivatives) were screened against liver fibrosis using an in vitro CCl4-induced injury model on cultured hepatocytes. IC50 values were calculated on the bases of LDH assay and cell viability assay. (3) Results: Among the eighteen compounds, compounds (10), (14) and (18) were selected on the basis of IC50 value, and compound (10) was the most potent and had the lowest IC50 value in the LDH assay (8.399 ± 0.23 uM) and cell viability assay (4.73 ± 0.37 uM). Next, these compounds were combined with MSCs using an in vitro hepatocytes injury culture and in vivo rat fibrotic model. The effect of the MSCs + compounds treatment on injured hepatocytes was evaluated using LDH assay, cell viability assay, GSH assay and real-time PCR analysis and immuno-staining for caspase-3. Significant reductions in LDH level, caspase-3 and apoptotic marker genes were noted in MSCs + compounds-treated injured hepatocytes. In vivo data also showed the increased homing of the MSCs, along with compounds after transplantation. Real-time PCR analysis and TUNEL assay results also support our study. (4) Conclusions: It was concluded that compounds (10), (14) and (18) can be used in combination with MSCs to reduce liver fibrosis.

A Winning New Combination? Toward Clinical Application in Oncology.

Immunotherapy has substantial attention in oncology due to the success of CTLA-4 and PD-1 inhibitors in the treatment of melanoma, lung cancer, head and neck cancer, renal cell carcinoma, and Hodgkin's lymphoma. A deeper understanding of interaction of tumor with its environment and the immune system provides best guide for oncology research. Recent studies in oncology have explained how a tumor alters antigen presentation, avoids detection, and activation of the host immune system to live and develop. Understanding the connections between the tumor and the immune system has resulted in several innovative therapy options. The extensive field of gene therapy has provided a number of cutting-edge medicines that are expected to play an important role in lowering cancer-related mortality. This article explains the history, important breakthroughs, and future prospects for three separate gene therapy treatment modalities: immunotherapy, oncolytic virotherapy, and gene transfer. Immunotherapies have completely changed how cancer is treated, especially for individuals whose condition was previously thought to be incurable. Examples include ACT (adoptive cell therapy) and ICB (immune checkpoint blockade). This review article will discuss the relationship between the immune response to cancer and the mechanisms of immunotherapy resistance. It will cover combination drugs authorized by the US Food and Drug Administration and provide a thorough overview of how these drugs are doing clinically right now. Cytokines, vaccines, and other soluble immunoregulatory agents, innate immune modifiers, ACT, virotherapy, and other treatment modalities will all be covered in detail.

Mixed [Formula: see text]-synthesis tracking control and disturbance rejection in a robotic digit of an impaired human hand for anthropomorphic coordination.

In a partially impaired anthropomorphic hand, maintaining the movement coordination of the robotic digits with the central nervous system (CNS) and natural digits is crucial for robust performance. A challenge in the control perspective of movement coordination of a human hand is finding methods robust to the disturbances in a well-posed control problem of a biomechanical model. We use visco-elastic dynamics in the human palm frame of reference to explore the biomechanics of movement coordination to solve this control problem. Our biomechanical model incorporates the time delay due to actuation force, parametric uncertainty, exogenous disturbances, and sensory noise to constitute a 21-degree of freedom model. A mixed [Formula: see text]-synthesis controller, considering the real parametric uncertainty, represents the CNS in the control paradigm. We consider the robotic finger's flexion movement when perturbed from the initial equilibrium. The controller provides feedback force at the joints to regulate the robotic finger movement. The index finger follows a reference trajectory of the joint angular position profile and stabilizes at a flexion angle of 1 rad/s at a time of 1 s. The main control objective is to keep the angular displacement of the finger joint constant when a disturbance force acts. We simulate the modeling scheme in MATLAB/ Simulink. The results demonstrate that our controller scheme is robust against the worst-case disturbance and achieves the desired performance value. Developing a biologically inspired neurophysiological controller with robust performance has many applications, including assistive rehabilitation devices, hand movement disorder diagnosis, and robotic manipulators.

Mpox in Young Woman with No Epidemiologic Risk Factors, Massachusetts, USA.

We describe a case of mpox characterized by a circularly distributed facial rash but no identified risk factors. Fomite transmission of monkeypox virus from contaminated linen at a massage spa was suspected. Clinicians should consider mpox in patients with consistent clinical syndromes, even in the absence of epidemiologic risk factors.

Built by epidemiologists for epidemiologists: an internal COVID-19 dashboard for real-time situational awareness in New York City.

Objective: New York City (NYC) experienced a large first wave of coronavirus disease 2019 (COVID-19) in the spring of 2020, but the Health Department lacked tools to easily visualize and analyze incoming surveillance data to inform response activities. To streamline ongoing surveillance, a group of infectious disease epidemiologists built an interactive dashboard using open-source software to monitor demographic, spatial, and temporal trends in COVID-19 epidemiology in NYC in near real-time for internal use by other surveillance and epidemiology experts. Materials and methods: Existing surveillance databases and systems were leveraged to create daily analytic datasets of COVID-19 case and testing information, aggregated by week and key demographics. The dashboard was developed iteratively using R, and includes interactive graphs, tables, and maps summarizing recent COVID-19 epidemiologic trends. Additional data and interactive features were incorporated to provide further information on the spread of COVID-19 in NYC. Results: The dashboard allows key staff to quickly review situational data, identify concerning trends, and easily maintain granular situational awareness of COVID-19 epidemiology in NYC. Discussion: The dashboard is used to inform weekly surveillance summaries and alleviated the burden of manual report production on infectious disease epidemiologists. The system was built by and for epidemiologists, which is critical to its utility and functionality. Interactivity allows users to understand broad and granular data, and flexibility in dashboard development means new metrics and visualizations can be developed as needed. Conclusions: Additional investment and development of public health informatics tools, along with standardized frameworks for local health jurisdictions to analyze and visualize data in emergencies, are warranted.

Solitary Retroperitoneal Neurofibroma Associated With Deep Vein Thrombosis in a 40-Year-Old Male.

A neurofibroma is a benign, non-encapsulated neoplasm of the peripheral nerve sheath. These tumors are a notorious manifestation of the autosomal dominant condition known as neurofibromatosis type 1, where they present as multiple, cutaneous masses with high malignant potential. On the contrary, benign solitary retroperitoneal neurofibromas (SRN) occur without any associated conditions and have rarely been documented. Our case is of a 40-year-old male who presented with a three-month history of painful calf swelling, refractory to over-the-counter painkillers which was later diagnosed as deep vein thrombosis (DVT). A computed tomography (CT) angiogram was done which revealed a mass in the retroperitoneum impinging on the inferior vena cava (IVC). Approximately one month later, the whole mass was surgically excised and histopathology confirmed the diagnosis of a neurofibroma. This case presentation proved to be novel as it highlights the evaluation and management of a rare SRN which resulted in extensive DVT.

Antibiotic consumption among hospitalized neonates and children in Punjab province, Pakistan.

BACKGROUND: Periodic surveillance of antibiotic consumption in the form of point prevalence studies is a quick and robust methodology to evaluate prescribing trends in hospitals. The current study was undertaken to document antibiotic consumption among neonates and children from hospitals in Pakistan. METHODS: This large multicenter study using the World Health Organization standardized methodology and AWaRe (Access, Watch, and Reserve) classification examined antibiotic consumption for suspected bacterial infection among neonates and children admitted hospitals in Punjab, Pakistan. RESULTS: A total of 708 beds of children wards of the 16 health facilities were examined. Almost all (97%) hospitalized children were prescribed antibiotics on the day of the assessment with 2.6 antibiotics per patient. The three most common indications were respiratory tract infections (31.58%), sepsis (26.52%), and prophylaxis for medical problems (10.30%). The three most frequently prescribed antibiotics were ceftriaxone (24.2%), amikacin (23.2%), and ampicillin (16.7%). Almost half of the antibiotics were prescribed from the 'Access' (49.5%) and 'Watch' (45.5%) categories under the AWaRe classification. However, no antimicrobial was prescribed from the 'Reserved' category. CONCLUSIONS: Our findings indicate that empirical antimicrobials use among hospitalized children is highly prevalent in Pakistan. The utilization of 'Watch' category of antimicrobials is frequent, stressing immediate action.

Chalcones: As Potent α-amylase Enzyme Inhibitors; Synthesis, In Vitro, and In Silico Studies.

BACKGROUND: The inhibition of α-amylase enzyme is one of the best therapeutic approach for the management of type II diabetes mellitus. Chalcone possesses a wide range of biological activities. OBJECTIVE: In the current study chalcone derivatives (1-16) were synthesized and evaluated their inhibitory potential against α-amylase enzyme. METHODS: For that purpose, a library of substituted (E)-1-(naphthalene-2-yl)-3-phenylprop-2-en-1-ones was synthesized by Claisen-Schmidt condensation reaction of 2-acetonaphthanone and substituted aryl benzaldehyde in the presence of base and characterized via different spectroscopic techniques such as EI-MS, HRESI-MS, 1H-, and 13C-NMR. RESULTS: Sixteen synthetic chalcones were evaluated for in vitro porcine pancreatic α-amylase inhibition. All the chalcones demonstrated good inhibitory activities in the range of IC50 = 1.25 ± 1.05 to 2.40 ± 0.09 µM as compared to the standard commercial drug acarbose (IC50 = 1.34 ± 0.3 µM). CONCLUSION: Chalcone derivatives (1-16) were synthesized, characterized, and evaluated for their α- amylase inhibition. SAR revealed that electron donating groups in the phenyl ring have more influence on enzyme inhibition. However, to insight the participation of different substituents in the chalcones on the binding interactions with the α-amylase enzyme, in silico (computer simulation) molecular modeling analyses were carried out.

COVID-19 Outbreak - New York City, February 29-June 1, 2020.

New York City (NYC) was an epicenter of the coronavirus disease 2019 (COVID-19) outbreak in the United States during spring 2020 (1). During March-May 2020, approximately 203,000 laboratory-confirmed COVID-19 cases were reported to the NYC Department of Health and Mental Hygiene (DOHMH). To obtain more complete data, DOHMH used supplementary information sources and relied on direct data importation and matching of patient identifiers for data on hospitalization status, the occurrence of death, race/ethnicity, and presence of underlying medical conditions. The highest rates of cases, hospitalizations, and deaths were concentrated in communities of color, high-poverty areas, and among persons aged ≥75 years or with underlying conditions. The crude fatality rate was 9.2% overall and 32.1% among hospitalized patients. Using these data to prevent additional infections among NYC residents during subsequent waves of the pandemic, particularly among those at highest risk for hospitalization and death, is critical. Mitigating COVID-19 transmission among vulnerable groups at high risk for hospitalization and death is an urgent priority. Similar to NYC, other jurisdictions might find the use of supplementary information sources valuable in their efforts to prevent COVID-19 infections.

Public Health Management of Persons Under Investigation for Ebola Virus Disease in New York City, 2014-2016.

During 2014-2016, the largest outbreak of Ebola virus disease (EVD) in history occurred in West Africa. The New York City Department of Health and Mental Hygiene (DOHMH) worked with health care providers to prepare for persons under investigation (PUIs) for EVD in New York City. From July 1, 2014, through December 29, 2015, we classified as a PUI a person with EVD-compatible signs or symptoms and an epidemiologic risk factor within 21 days before illness onset. Of 112 persons who met PUI criteria, 74 (66%) sought medical care and 49 (44%) were hospitalized. The remaining 38 (34%) were isolated at home with daily contact by DOHMH staff members. Thirty-two (29%) PUIs received a diagnosis of malaria. Of 10 PUIs tested, 1 received a diagnosis of EVD. Home isolation minimized unnecessary hospitalization. This case study highlights the importance of developing competency among clinical and public health staff managing persons suspected to be infected with a high-consequence pathogen.

Active Monitoring of Travelers for Ebola Virus Disease-New York City, October 25, 2014-December 29, 2015.

The CDC recommended active monitoring of travelers potentially exposed to Ebola virus during the 2014 West African Ebola virus disease outbreak, which involved daily contact between travelers and health authorities to ascertain the presence of fever or symptoms for 21 days after the travelers' last potential Ebola virus exposure. From October 25, 2014, to December 29, 2015, the New York City Department of Health and Mental Hygiene (DOHMH) monitored 5,359 persons for Ebola virus disease, corresponding to 5,793 active monitoring events. Most active monitoring events were in travelers classified as low (but not zero) risk (n = 5,778; 99%). There were no gaps in contact with DOHMH of ≥2 days during 95% of active monitoring events. Instances of not making any contact with travelers decreased after CDC began distributing mobile telephones at the airport. Ebola virus disease-like symptoms or a temperature ≥100.0°F were reported in 122 (2%) active monitoring events. In the final month of active monitoring, an optional health insurance enrollment referral was offered for interested travelers, through which 8 travelers are known to have received coverage. Because it is possible that active monitoring will be used again for an infectious threat, the experience we describe might help to inform future such efforts.

Raising public awareness of aphasia in southern Ontario, Canada: A survey.

PURPOSE: Despite the relatively high prevalence of aphasia, research indicates that, world-wide, public awareness of aphasia is lacking. Of the surveys that have been conducted internationally, none has studied the Canadian public's awareness of aphasia. The purpose of the present survey was to assess public awareness and basic knowledge of aphasia of individuals in southern Ontario, Canada. METHOD: Using the same questionnaire that has been used in other countries, face-to-face surveys were conducted in public places (e.g. parks) at various locations in southern Ontario. Respondents were asked questions pertaining to their awareness and knowledge of aphasia. The number of surveys retained for analysis was 831. In addition to an evaluation of public awareness and knowledge of aphasia, the potential influences of age, gender, and occupation were analysed. For those who had heard of aphasia, questions were asked to determine how or where they had heard of aphasia. RESULT: Consistent with the literature, overall public awareness and basic knowledge of aphasia in southern Ontario was found to be limited. The factors of age, gender and occupation were found to influence the results. CONCLUSION: This investigation supports the need for better promotion of aphasia awareness to the public in southern Ontario and, by extension, in Canada.

The effect on student performance of scrambling questions and their stems in medical colleges admission tests.

Assessment is an indispensable part of an educational program. Multiple Choice Questions (MCQs) is an objective tool of assessment provided cheating is controlled. A method employed to reduce the chance of cheating is to scramble the sequence of the MCQs and responses in multiple papers having the same content. It is assumed that the performance of students is mainly dependent on the difficulty of the items and not the order in which they are placed within the instrument. The marks obtained by 1,02,211 candidates sitting in Medical Colleges Admission Test (MCAT) from 2008 to 2011 and given similar-content but scrambled-sequence question paper codes were analyzed using parametric tests. A significant difference amongst the mean marks of candidates in the different codes of MCAT 2008 (F = 22.15, p < 0.001) and MCAT 2011 (F = 3.85, p = 0.009) was identified. No significant difference was found in the mean marks of the candidates' each year for different codes in each centre.

A Thermostable Crude Endoglucanase Produced by Aspergillus fumigatus in a Novel Solid State Fermentation Process Using Isolated Free Water.

Aspergillus fumigatus was grown on chopped wheat straw in a solid state fermentation (SSF) process carried out in constant presence of isolated free water inside the fermentation chamber. The system allowed maintaining a constant vapor pressure inside the fermentor throughout the fermentation process. Crude endoglucanase produced by A. fumigatus under such conditions was more thermostable than previously reported enzymes of the same fungal strain which were produced under different conditions and was also more thermostable than a number of other previously reported endoglucanases as well. Various thermostability parameters were calculated for the crude endoglucanase. Half lives (T(1/2)) of the enzyme were 6930, 866, and 36 min at 60°C, 70°C, and 80°C, respectively. Enthalpies of activation of denaturation (ΔH(D)*) were 254.04, 253.96, and 253.88 K J mole(-1), at 60°C, 70°C and 80°C, respectively, whereas entropies of activation of denaturation (ΔS(D)*) and free energy changes of activation of denaturation (ΔG(D)*) were 406.45, 401.01, and 406.07 J mole(-1) K(-1) and 118.69, 116.41, and 110.53 K J mole(-1) at 60°C, 70°C and 80°C, respectively.

Two oppositely oriented arrays of low-affinity recognition sites in oriC guide progressive binding of DnaA during Escherichia coli pre-RC assembly.

The onset of chromosomal DNA replication requires highly precise and reproducible interactions between initiator proteins and replication origins to assemble a pre-replicative complex (pre-RC) that unwinds the DNA duplex. In bacteria, initiator protein DnaA, bound to specific high- and low-affinity recognition sites within the unique oriC locus, comprises the pre-RC, but how complex assembly is choreographed to ensure precise initiation timing during the cell cycle is not well understood. In this study, we present evidence that higher-order DnaA structures are formed at oriC when DnaA monomers are closely positioned on the same face of the DNA helix by interaction with two oppositely oriented essential arrays of closely spaced low-affinity DnaA binding sites. As DnaA levels increase, peripheral high-affinity anchor sites begin cooperative loading of the arrays, which is extended by sequential binding of additional DnaA monomers resulting in growth of the complexes towards the centre of oriC. We suggest that this polarized assembly of unique DnaA oligomers within oriC plays an important role in mediating pre-RC activity and may be a feature found in all bacterial replication origins.

Developing the outcomes of a baccalaureate of dental surgery programme.

BACKGROUND: Curriculum broadly falls into two categories, prescriptive and outcome-based. In the prescriptive curricula emphasis is placed on teaching with generally little integration between subjects and across disciplines. Currently, universities in Pakistan are undergoing a cultural change in the curricular design in order to apply an outcome-based learning instead of prescriptive teaching. Regionally, the need for change was recognised on account of the vast body of evidence available internationally. In order to bring about a shift towards an outcome based curriculum in the 4-year BDS programme, we first need to specify the outcomes/traits that the dental health professionals should be able to demonstrate upon leaving the programme. This paper describes the process and outcome of arriving at the desired consensus through a series of workshops involving all stakeholders including students, community members, teaching faculty, programme directors and representatives of the dental health industry. METHODS: A series of workshops were conducted between September 2009 to February 2010 in all of the 18 disciplines of basic and dental sciences individually and then collectively. A questionnaire sought responses from the participants regarding their perception about the status of the current BDS curriculum and their understanding of an outcome-based integrated curriculum, as well as whether such an integrated curriculum should be adopted or not? In the second half of the workshop through brainstorming and Delphi technique, the outcomes in terms of measurable traits that should be possessed by a graduate dental health professional entering community service were enlisted. The pre- and post-workshop questionnaire scores were entered into SPSS-16 and paired sample t-test as well as chi-square test were applied. Cron back alpha value of < 0.05 was taken as statistically significant. Secondly, the outcomes developed in each workshop were entered into Ethnograph and common outcomes of the 4-year BDS programme were extracted. RESULTS: In total, 234 participants attended the workshop over a period of five months in 18 discipline-wise workshops and four integrated workshops involving faculty members of all disciplines. Results indicate clearly that the workshop resulted in an attitude shift of the participants and their perception of the current curriculum and the need and rationale for a move towards an outcome-based curriculum. The 30 outcomes identified were grouped under two categories namely 'clinical skills' and 'professional behaviours'. CONCLUSION: Defining the final programme outcomes is only the initial step in developing an outcome-based, objective, integrated curriculum which will require considerable work in the future.

Relationship of awards in multiple choice questions and structured answer questions in the undergraduate years and their effectiveness in evaluation.

BACKGROUND: A number of evaluation tools for assessing the cognitive and affective domains in accordance with Bloom's taxonomy are available for summative assessment. At the University of Health Sciences, Lahore, Multiple Choice Questions (MCQs) and Structured Answer Questions (SAQs) are used for the evaluation of the cognitive domain at all six hierarch levels of taxonomy using the tables of specifications to ensure content validity. The rationale of having two evaluation tools seemingly similar in their evaluative competency yet differing in feasibility of construction, administration and marking is being challenged in this study. METHODS: The MCQ and SAQ awards of the ten percent sample population amounting to 985 students in fifteen Medical and Dental Colleges across Punjab were entered into SPSS-15 and correlated according to the cognitive and affective level of assessment in relation to the Bloom's taxonomy and their grouping in the Tables of Specifications, using parametric tests. 3494 anonymously administered questionnaires were analyzed using ethnograph. RESULTS: No statistically significant difference was found in the mean marks obtained by the students when MCQs and SAQs were compared according to their groupings in the Tables of Specifications at all levels of cognitive hierarchical testing. End-of-yearcognitive level testing targets set were not met and more questions were set at the lower cognitive testing levels. Expenses incurred in setting MCQs and SAQs were comparable but conduct and assessment costs for MCQs and SAQs were 6% and 94% of the total respectively. In both MCQs and SAQs students performed better at higher cognitive testing levels whereas the SAQs and MCQs were able to marginally test the lower levels of affective domain only. Student's feedback showed that attempting MCQs required critical thinking, experience and practice. CONCLUSION: MCQs are more cost effective means at levels of cognitive domain assessment.