Monolithic silicon microlens arrays for far-infrared astrophysics.

Future far-infrared astrophysics observatories will require focal plane arrays containing thousands of ultrasensitive, superconducting detectors, each of which require efficient optical coupling to the telescope fore-optics. At longer wavelengths, many approaches have been developed, including feedhorn arrays and macroscopic arrays of lenslets. However, with wavelengths as short as 25 µm, optical coupling in the far infrared remains challenging. In this paper, we present an approach to fabricate far-infrared monolithic silicon microlens arrays using grayscale lithography and deep reactive ion etching. The fabricated microlens arrays presented here are designed for two different wavebands: 25-40 µm and 135-240 µm. The microlens arrays have sags as deep as 150 µm, are hexagonally packed with a pixel pitch of 900 µm, and have an overall size as large as 80 by 15 mm. We compare an as-fabricated lens profile to the design profile and calculate that the fabricated lenses would achieve 84% encircled power for the designed detector, which is only 3% less than the designed performance. We also present methods developed for antireflection coating microlens arrays and for a silicon-to-silicon die bonding process to hybridize microlens arrays with detector arrays.

Role of tumor microenvironment in cancer progression and therapeutic strategy.

Cancer is now considered a tumor microenvironment (TME) disease, although it was originally thought to be a cell and gene expression disorder. Over the past 20 years, significant advances have been made in understanding the complexity of the TME and its impact on responses to various anticancer therapies, including immunotherapies. Cancer immunotherapy can recognize and kill cancer cells by regulating the body's immune system. It has achieved good therapeutic effects in various solid tumors and hematological malignancies. Recently, blocking of programmed death-1 (PD-1), programmed death-1 ligand-1 (PD-L1), and programmed death Ligand-2 (PD-L2), the construction of antigen chimeric T cells (CAR-T) and tumor vaccines have become popular immunotherapies Tumorigenesis, progression, and metastasis are closely related to TME. Therefore, we review the characteristics of various cells and molecules in the TME, the interaction between PD-1 and TME, and promising cancer immunotherapy therapeutics.

Lymphoscintigraphy Using Tilmanocept Detects Multiple Sentinel Lymph Nodes in Melanoma Patients.

BACKGROUND: Technetium-99m-labeled Tilmanocept, a multivalent mannose, is readily internalized by the CD206 surface receptor on macrophages and dendritic cells which are abundantly present in lymph nodes. We want to examine the drainage patterns of Technetium-99m-labeled Tilmanocept to sentinel lymph nodes (SLNs) in melanoma patients following the 10% rule. METHODS: Multi-center retrospective review of patients with cutaneous melanoma undergoing SLN biopsy using Technetium-99m-labeled Tilmanocept between 2008 and 2014 was conducted. Statistical methods were used for data analyses. RESULTS: Of the 564 patients (mean age of 60.3 and 62% male) with preoperative lymphoscintigraphy showing at least one SLN, several primary tumor sites were included: 27% head/neck, 33% trunk, 21% upper extremity and 19% lower extremity. For the head/neck primary site, 36.5% of patients had multiple draining basins; for the trunk site, 36.4% of patients; for the upper extremity site, 13% of patients; and for the lower extremity, 27.4% of patients. A median of 3 (range 1-18) SLNs were identified and resected. Overall, 78% of patients had >1 SLN identified by Technetium-99m-labeled Tilmanocept. In a multivariate model, patients with >1 SLN were significantly associated with age, Breslow depth, tumor location and higher AJCC tumor stage. A total of 17.7% of patients (100/564) had a positive SLN identified. A total of 145 positive SLNs were identified out of 1,812 SLNs with a positive SLN rate of 8%. Positive SLN status was significantly associated with younger age, greater Breslow depth, mitosis rate, higher AJCC tumor stage, presence of ulceration and angiolymphatic invasion. CONCLUSIONS: Using the 10% rule, Technetium-99m-labeled Tilmanocept detects multiple SLNs in most melanoma patients.

Reoperation Following Zone II Flexor Tendon Repair.

BACKGROUND: The goal of zone II flexor tendon surgery is to perform a repair with sufficient strength to withstand the forces encountered during rehabilitation. Postoperative rerupture and adhesion formation may lead to reoperation. This study aimed to determine the factors associated with reoperation after primary zone II flexor tendon repair. METHODS: In this retrospective case series, a total of 252 fingers in 201 patients underwent zone II flexor tendon repair. A medical record review was performed to collect data regarding patient demographics, injury and treatment characteristics and postoperative complications including reoperation. Reoperation was defined as any unplanned surgical procedure performed after initial flexor tendon repair. RESULTS: There were 49 fingers (19%) in 42 patients that underwent reoperation at a median of 5.5 (interquartile range: 2.8-7.9) months. Older age, workers' compensation, and a Kessler-type repair of the flexor digitorum profundus were independently associated with reoperation. CONCLUSIONS: In vitro studies suggest that Kessler-type repairs are inferior compared with other suture configurations. Our study demonstrates a clinical correlation to these biomechanical studies. Our results suggest that Kessler-type repairs are inferior compared with non-Kessler-type repairs, due to postoperative complications requiring secondary surgeries.

Evaluation of panel of neutralising murine monoclonal antibodies and a humanised bispecific antibody against influenza A(H1N1)pdm09 virus infection in a mouse model.

The influenza A (H1N1) pdm09 virus attracted public attention because of its high prevalence. The annual global morbidity and mortality rates of influenza remain high despite the application of influenza vaccines and antiviral drugs, which indicates the urgent need to identify a more effective strategy for controlling and treating A(H1N1) pdm09 influenza infection. To produce a highly effective therapeutic with broad specificity for A(H1N1) pdm09 influenza viruses, we generated 15 murine monoclonal antibodies (mAbs) via hybridoma technology: 11 mAbs demonstrated 20-100% therapeutic protection in a mouse model of A(H1N1) pdm09 infection at a single dose of 10 mg/kg. A humanised bispecific antibody (Bis-Hu11-1) generated based on the mAbs 3D2 and 3D11, combining the specificities of the two mAbs, was also effective in preventing and treating A(H1N1) pdm09 infection in a mouse model. Bis-Hu11-1 demonstrated hemagglutination inhibition (HI) activity against the escape mutants generated by its parental mAbs that resulted in the obvious reduction in the HI activity of the parental mAbs. In summary, we generated a panel of neutralising mAbs against A(H1N1) pdm09 influenza virus. This study presents a promising method for developing neutralising antibodies that potentially target a series of antigenically diverse influenza viruses.

Lyme disease presenting as persistent severe photophobia.

Long-term photophobia in children that has no obvious cause is uncommon and presents a diagnostic dilemma. It may produce significant discomfort and result in social isolation and school absence. We present the case of a 5-year-old boy who presented with chronic photophobia due to interstitial keratitis that was the result of Lyme disease.

Factors associated with revision surgery for olecranon bursitis after bursectomy.

BACKGROUND: The primary aim of our study was to identify the factors associated with revision surgery after bursal excision in patients with olecranon bursitis. The secondary aims were to describe the revision rate after bursectomy and to assess which factors are associated with flap surgery after bursectomy and describe the most common complications after bursectomy of the olecranon bursa. METHODS: We included 191 adult patients with olecranon bursitis who underwent olecranon bursa excision between January 2002 and October 2018. Patients who were pregnant, patients with incomplete records of the primary surgical procedure, and patients who underwent bursectomy during elbow arthroplasty were excluded. After manual chart review, we found that 22 patients had undergone revision surgery. Bivariate analysis was performed to assess the association between revision surgery and patient characteristics, comorbidities, and clinical characteristics. Additionally, we collected data regarding postoperative complications and intraoperative variables such as the use of drains, vacuum assisted closure therapy, and flap surgery. RESULTS: The overall revision rate in our cohort was 11.5% (22 of 191 patients). Bivariate analysis showed that patients who underwent revision surgery were more frequently women (P = .004), more often had a history of ipsilateral (P = .020) or contralateral (P = .012) olecranon bursitis, and more often received a diagnosis of rheumatoid arthritis (P = .001) or diabetes mellitus (P = .019). The most common complications were delayed wound healing (n = 8, 4.2%) and osteomyelitis (n = 8, 4.2%). Flap surgery was performed in 5 patients (2.6%). Bivariate analysis showed that patients with rheumatoid arthritis underwent flap surgery more frequently (P = .011). CONCLUSION: The revision rate after bursectomy for olecranon bursitis was 11.5% (22 of 191 patients). Patients with rheumatoid arthritis, diabetes mellitus, or a history of ipsilateral and contralateral olecranon bursitis and female patients underwent revision surgery after bursectomy for olecranon bursitis more frequently. In addition, patients with rheumatoid arthritis underwent flap surgery after bursectomy more frequently.

Fingertip Infections.

The fingertip is the most common site of infections in the hand, which frequently are encountered by surgeons, dermatologists, and emergency and primary providers. Their mismanagement may have serious consequences. This review discusses the unique anatomy of the volar fingertip pulp and perionychium and reviews pathophysiology and treatment of acute and chronic paronychia, including the decision for surgical versus medical management, choice of antibiotics, incisional techniques, and postincisional care. Felons and the evidence regarding their management are reviewed. Several infectious, rheumatologic, and oncologic conditions that may mimic common fingertip infections and about which the managing provider must be aware are presented.

Evaluating the Effects of COVID-19 on Plastic Surgery Emergencies: Protocols and Analysis From a Level I Trauma Center.

BACKGROUND: The COVID-19 crisis has brought many unique challenges to the health care system. Across the United States, social distancing measures have been put in place, including stay-at-home (SAH) orders, to combat the spread of this infection. This has impacted the type and volume of traumatic injuries sustained during this time. Meanwhile, steps have been taken in our health care system to assure that adequate resources are available to maintain a high standard of patient care while recognizing the importance of protecting health care providers. Using comparative data, we aim to describe the trends in traumatic injuries managed by our plastic surgery service and detail the changes in consultation policies made to minimize provider exposure. METHODS: A retrospective chart review was performed of all plastic surgery emergencies at our institution during the 3 weeks preceding the issuance of SAH orders in Chicago and the 3 weeks after. The electronic medical record was queried for patient age, type and mechanism of injury, location where injury was sustained, presence of domestic violence, length of inpatient hospital stays, and treatment rendered. The two 3-week periods were then comparatively analyzed to determine differences and trends in these variables and treatment rendered. The 2 periods were then comparatively analyzed to determine differences and trends in these variables. RESULTS: There was a significant decrease in trauma consults since the issuance of SAH (88 pre-SAH vs 62 post-SAH) with a marked decrease in trauma-related hand injuries. There was an increase in the percentage of assault-related injuries including those associated with domestic violence, whereas there was an overall decrease in motor vehicle collisions. There was no notable change in the location where injuries were sustained. Significantly fewer patients were seen by house staff in the emergency room, whereas those requiring surgical intervention were able to receive care without delay. CONCLUSIONS: Stay-at-home orders in Chicago have impacted traumatic injury patterns seen by the Section of Plastic and Reconstructive Surgery at a level I Trauma Center. Safe and timely care can continue to be provided with thorough communication, vigilance, and guidance from our colleagues.

The role of bacterial biofilm and mechanical forces in modulating dental implant failures.

Currently many assume that bacteria are the primary etiological factor associated with failure of titanium dental implants. However, emerging data indicates a possible role for mechanical forces in implant failure. This study is based on the hypothesis that the synergistic effect of mechanical forces and bacterial biofilm can lead to surface damage resulting in in vivo release of metallic particles. The primary aim of the study was to develop a dynamic fatigue test method for dental implants immersed in wet environments such as; (i) 0.01 M phosphate buffer saline (PBS); (ii) lactic acid (pH = 5); (iii) bacterial polyculture. Four dental implants each were subjected to fatigue loading from 45 N to 450 N at 4 Hz for 2 million cycles while immersed in (i) PBS (negative control); (ii) bacterial culture (test); and (iii) lactic acid (positive control). Post-testing, optical microscopy, x-ray photoelectron spectroscopy, and electrochemical corrosion tests were performed to evaluate the surface morphology, chemistry, and potential, respectively, of titanium implants. Post-testing, surface discoloration was evident in all three groups. However, the surface damage was further established in XPS analyses of test specimens, which showed that the interplay of bacterial biofilm and mechanical forces resulted in thinning of the TiO2. Lower corrosion potential (Ecorr) of the test specimens compared to positive and negative controls also illustrated damage to the oxide layer. However, other electrochemical parameters such as linear polarization resistance (LPR) and corrosion rate (CR) were comparable among the groups indicating the corrosion resistance post-testing. The synergistic effect of cyclic occlusal loading and bacteria biofilm could negatively affect the surface of titanium dental implants.

Can Oral Bacteria and Mechanical Fatigue Degrade Zirconia Dental Implants in Vitro?

Zirconia (ZrO2) is an emerging alternative to titanium for dental implant systems due to its material properties including high mechanical strength and chemical stability. However, oral environmental factors such as bacterial adhesion and mechanical fatigue may trigger low-temperature degradation of ZrO2, leading to reduced mechanical strength and potential implant fracture. Although failure modes of ZrO2 in orthopedic applications have been studied, they have yet to be thoroughly investigated in the context of dental implant systems. Thus, the goal of the present study was to assess the surface of ZrO2 dental implants for signs of degradation after exposure to oral bacteria and oral bacteria in combination with mechanical fatigue. ZrO2 dental implants were subjected to 30-day immersion in (i) early or (ii) late colonizing oral bacteria or (iii) were mechanically loaded for 2 × 106 cycles with oral bacteria in circulation. Optical microscopy, Raman microscopy, and X-ray photoelectron spectroscopy (XPS) were used to evaluate the surface morphology, phase composition, and chemical composition, respectively. Post-immersion, all implants exhibited minimal changes in surface features, and all loaded implants survived cyclic fatigue tests. All implants had <1% monoclinic phase at the collar, junction, and screw regions, excluding the screw threads, for which monoclinic phase was significantly higher but <10%. XPS revealed an increase in carbon- and nitrogen-based organic debris on the implants exposed to early colonizers as compared to those immersed in late colonizers or synergistically with mechanical loading. Within the limitations of the present study, ZrO2 is a suitable alternative material for dental implant systems based on its ability to resist both physical and chemical degradation imposed by oral bacteria and applied cyclic loads.

Development and Characterization of Neutralizing Antibodies Against Zaire Ebolavirus Glycoprotein and Protein 40.

BACKGROUND/AIMS: Monoclonal antibodies (mAbs) are presently the most promising treatment against Ebola virus disease (EVD), and cocktail of two or more antibodies likely confers protection through complementary mechanisms. Zaire Ebolavirus (EBOV) glycoprotein (GP) and viral protein 40 (VP40) are targets for designing neutralizing antibodies. Currently, the antiviral therapeutics of mAb-cocktails are still limited solely to anti-GP antibodies，there is no Abs cocktail against Zaire EBOV GP and VP40, which both have important interactions with host cellular membrane. METHODS: We used hybridoma technology to produce anti-Zaire EBOV GP mAb against GP receptor binding domain, and anti-Zaire EBOV VP40 mAbs against the N-terminal domain, the C-terminal domain, respectively; synthesized Zaire EBOV transcription and replication competent virus like particles (trVLPs), which model even all aspects of the EBOV life cycles in order to evaluate the anti-viral effect of mAbs. Then, we characterized the anti- Zaire EBOV trVLPs effect of anti-GP and VP40 mAbs in vitro by real time-PCR, immunofluorescence assay and western blot analysis. RESULTS: Our results demonstrate that anti-GP or anti-VP40 mAbs effectively inhibit trVLPs replication. The cocktails of anti-GP and anti-VP40 mAbs, or between anti-VP40 mAbs, had synergistic anti-trVLPs effect. Meanwhile, the detailed DNA and amino acid sequences of the mAbs were checked. CONCLUSION: The study verifies neutralizing efficacy of anti-GP or anti-VP40 mAb, report promising cocktail of anti-GP and anti-VP40 mAb, or cocktail of two anti-VP40 mAbs. To our knowledge, this is the first account to report the important anti-viral effect of cocktails of anti-GP and anti-VP40 mAbs in vitro.

Multifaceted roles of environmental factors toward dental implant performance: Observations from clinical retrievals and in vitro testing.

OBJECTIVE: Oral bacteria and periodontal pathogen have been predominantly linked with early- and late- stage failures of titanium (Ti) dental implants (DI) respectively. This study is based on the hypothesis that bacterial colonization can damage the surface oxide (TiO2) layer. Early-failed DI were compared with DI post-in vitro immersion in early colonizing oral bacteria; late failed DI were weighed against DI immersed in late colonizing anaerobic pathogens. METHODS: Retrieval analysis: Seven early- stage failed implants with five of them connected to healing abutments (HAs), and ten late- stage failed retrievals were subjected to surface analysis. Bacteria immersion test: Three dental implants each were immersed in polycultures containing (i) early colonizers (Streptococcus mutans, S. salivarius, S. sanguinis) (ii) late colonizers (Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans). The implants were immersed for 30 days to simulate the healing period and bacterial biofilm adhesion. Optical microscope, x-ray photoelectron spectroscopy (XPS), and electrochemical test were performed to analyze the surface- morphology, chemistry, and potential respectively. RESULTS: Early colonizers inflicted surface morphological damage (discoloration and pitting). Even though, XPS detected thinner oxide layer in 2/3 early retrievals, XPS and electrochemical tests illustrated that the TiO2 layer was intact in HAs, and in DI post- immersion. Late colonizers also caused similar morphological damage (discoloration and pitting), while mechanical wear was evident with scratches, cracks, and mechanical fracture observed in late-stage retrievals. XPS indicated thinner oxide layer in late-stage retrievals (3/4), and in DI post-immersion in late colonizers. This was reflected in electrochemical test results post-immersion but not in the late-stage retrievals, which suggested an intact surface with corrosion resistance. SIGNIFICANCE: This study concluded that bacteria could negatively affect implant surface with late colonizers demonstrating more pronounced damage on the surface morphology and chemistry.