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Neurophotonics was launched in 2014 coinciding with the launch of the BRAIN Initiative focused on development of technologies for advancement of neuroscience. For the last seven years, Neurophotonics' agenda has been well aligned with this focus on neurotechnologies featuring new optical methods and tools applicable to brain studies. While the BRAIN Initiative 2.0 is pivoting towards applications of these novel tools in the quest to understand the brain, this status report reviews an extensive and diverse toolkit of novel methods to explore brain function that have emerged from the BRAIN Initiative and related large-scale efforts for measurement and manipulation of brain structure and function. Here, we focus on neurophotonic tools mostly applicable to animal studies. A companion report, scheduled to appear later this year, will cover diffuse optical imaging methods applicable to noninvasive human studies. For each domain, we outline the current state-of-the-art of the respective technologies, identify the areas where innovation is needed, and provide an outlook for the future directions.

Aryl‐maleimides undergo a novel [2+4]‐photodimerization instead of the expected [2+2]‐photodimerization under both direct irradiation with visible light and under sensitized energy transfer conditions. This new excited state reactivity in aryl‐maleimides is deciphered through photochemical, photophysical, and spectroscopic studies. The stereochemistry of the photodimer depends on the type of non‐bonding interactions prevalent during photodimerization which is in turn dictated by the substituents on the maleimide ring. More importantly, the stereochemistry of the photodimer formed is complementary to the product observed under thermal conditions. [ABSTRACT FROM AUTHOR]

This account highlights the role of restricted bond rotations in influencing the excited-state reactivity of organic molecules. It highlights the photochemical reactivity of various organic molecules and the design strategies that could be exploited by chemists to utilize restricted bond rotations to uncover new excited-state reactivity and to achieve selectivity. 1 Introduction. 2 NEER-Principle and Restricted Bond Rotations in the Excited State 3 [2+2]-Photocycloaddition of Enamides 4 [3+2]-Photocycloaddition vs. Paternò–Büchi Reaction of Enamides 5 Divergent Photoreactivity of Enones Dictated by Restricted Bond Rotations: Norrish–Yang reactions vs. 6π-Photocyclization 6 Divergent Photoreactivity of Imides with Alkenes: [2+2]-Photocycloaddition vs. Photoene Reaction 7 Summary and Outlook [ABSTRACT FROM AUTHOR]

Intermolecular [2+2]‐photocycloaddition of atropisomeric phenyl maleimide has been evaluated with substituted alkenes with complete control over regiochemistry. We were also successful in carrying out atropselective reactions with the removal of axial chirality leading to enantio‐enriched photoproducts. Based on detailed photophysical studies, a mechanistic rationale is proposed for the observed selectivity. [ABSTRACT FROM AUTHOR]

Citation Winger EE, Reed JL, Ashoush S, El-Toukhy T, Ahuja S, Taranissi M. Elevated preconception CD56+16+ and/or Th1:Th2 levels predict benefit from IVIG therapy in subfertile women undergoing IVF. Am J Reprod Immunol 2011; 66: 394-403 Problem We sought to answer two questions: First, is there a group of patients who benefit from intravenous immunoglobulin (IVIG) in IVF? Second can this group of patients be identified by preconception blood testing? Method of study A total of 202 IVF cycles in subfertile women were divided into four groups. Group I: 62 cycles with preconception Th1:Th2 ratio and/or % CD56+ cell elevation using IVIG; Group II: 27 cycles with similar Th1:Th2 and/or % CD56+ cell elevation not using IVIG; Group III: 71 cycles with normal Th1:Th2 and/or % CD56+ cell levels using IVIG; Group IV: 42 cycles with normal Th1:Th2 and % CD56+ levels not using IVIG. These groups were similar with regard to patient age, diagnosis, and past failure history. Results The implantation rate (number of gestational sacs per embryo transferred, with an average of two embryos transferred per cycle) was 45% (55/123), 22% (12/54), 54% (75/139), and 48% (40/84) for Groups I-IV, respectively. The clinical pregnancy rate (fetal heart activity per IVF cycle started) was 61% (38/62), 26% (7/27), 69% (49/71), and 71% (30/42), respectively. The live birth rate was 58% (36/62), 22% (6/27), 61% (43/71), and 71% (30/42), respectively, and the live birth per embryo transferred was 40% (49/123), 13% (7/24), 43% (60/139), and 48% (40/84), respectively. There was a significant improvement in implantation, clinical pregnancy, live birth rate and live birth rate per embryo transferred for Group I versus Group II ( P = 0.0032, 0.0021, 0.0017, and 0.0002, respectively) and for Group II versus Group IV ( P = 0.0021, 0.0002, <0.0001 and <0.0001, respectively). There was no significant difference in success rates between Groups I and III ( P = 0.085, 0.23, 0.45, 0.34, respectively) and between Groups III and IV ( P = 0.22, 0.48, 0.17, 0.31, respectively). Conclusion In subfertile women with preconception Th1:Th2 and/or % CD56+ cell elevation, IVF success rates are low without IVIG therapy but significantly improve with IVIG therapy. In patients with normal Th1:Th2 and normal CD56+ cell levels, IVF success rates were not further improved with IVIG therapy. IVIG may be a useful treatment option for patients with previous IVF failure and preconception Th1:Th2 and/or NK elevation. Preconception immune testing may be a critical tool for determining which patients will benefit from IVIG therapy. Prospective controlled studies (preferably double-blind, stratified, and randomized) are needed for confirmation. [ABSTRACT FROM AUTHOR]

Citation Winger EE, Reed JL, Ashoush S, El-Toukhy T, Ahuja S, Taranissi M. Birth defect rates in women using Adalimumab (Humira®) to treat immunologic-based infertility in IVF patients. Am J Reprod Immunol 2011; 66: 237-241 Problem This study compares the birth defect rate in women using preconception TNF-α inhibitor (Adalimumab) during an in vitro fertilization (IVF) cycle to a similar population of women not using these immunologic therapies. Method of study One hundred subfertile women aged ≤38 years experienced ongoing pregnancies of which 36 resulted in twin pregnancies (136 babies). These successful cycles were divided into two different treatment groups: group I comprised 31 cycles (23 ICSI) using preconception Adalimumab (Humira) with or without pre- or post-conception intravenous immunoglobulin (IVIG) (last dose of Humira given 65.3 ± 41.5 days before embryo transfer). Group II comprised 69 cycles (58 ICSI) with no exposure to Humira or IVIG. Group I included all eligible fresh cycles containing at least five 5-celled embryos on day 3. Group II had similar entry criteria, but eligible cycles were randomly selected owing to a larger population size. Patients were later contacted by the clinic for neonatal health information. Results Delivery outcomes were as follows: group I experienced one case of DiGeorge syndrome (chromosome 22 deletion) that was electively terminated out of 41 babies (10 sets of twins) delivered. Group II experienced one case of neonatal heart defect and another case of Edward's syndrome (Trisomy 18) out of 95 babies (26 sets of twins) delivered. The anomaly rate was 2.44% (1/41) and 2.11% (2/95) for groups I and II, respectively, comparable to the expected birth defect rate for the normal IVF population. Conclusion Preconception TNF-α inhibitor does not appear to increase the birth defect rate in women undergoing IVF. A larger, clinical trial with blinded delivery assessment is needed to confirm these safety conclusions. [ABSTRACT FROM AUTHOR]

Problem The purpose of this study was to investigate whether treatment with TNF-α inhibitors and/or intravenous immunoglobulin (IVIG) increases in vitro fertilization (IVF) success rates among young (<38 years) women with infertility and T helper 1/T helper 2 cytokine elevation. Method of study Seventy-five sub-fertile women with Th1/Th2 cytokine elevation were divided into four groups: Group I: Forty-one patients using both IVIG and Adalimumab (Humira®), Group II: Twenty-three patients using IVIG, Group III: Six patients using Humira®, and Group IV: Five patients using no IVIG or Humira®. Results The implantation rate (number of gestational sacs per embryo transferred, with an average of two embryos transferred by cycle) was 59% (50/85), 47% (21/45), 31% (4/13) and 0% (0/9) for groups I, II, III and IV respectively. The clinical pregnancy rate (fetal heart activity per IVF cycle started) was 80% (33/41), 57% (13/23), 50% (3/6) and 0% (0/5) and the live birth rate was 73% (30/41), 52% (12/23), 50% (3/6) and 0% (0/5) respectively. There was a significant improvement in implantation, clinical pregnancy and live birth rates for group I versus group IV ( P = 0.0007, 0.0009, and 0.003, respectively) and for group II versus group IV ( P = 0.009, 0.04 and 0.05, respectively). Conclusion The use of a TNF-α inhibitor and IVIG significantly improves IVF outcome in young infertile women with Th1/Th2 cytokine elevation. [ABSTRACT FROM AUTHOR]

Problem: We sought to answer two questions: First, is there a group of patients who benefit from intravenous immunoglobulin (IVIG) in IVF? Second can this group of patients be identified by preconception blood testing?, Method of Study: A total of 202 IVF cycles in subfertile women were divided into four groups. Group I: 62 cycles with preconception Th1:Th2 ratio and/or % CD56(+) cell elevation using IVIG; Group II: 27 cycles with similar Th1:Th2 and/or % CD56(+) cell elevation not using IVIG; Group III: 71 cycles with normal Th1:Th2 and/or % CD56(+) cell levels using IVIG; Group IV: 42 cycles with normal Th1:Th2 and % CD56(+) levels not using IVIG. These groups were similar with regard to patient age, diagnosis, and past failure history., Results: The implantation rate (number of gestational sacs per embryo transferred, with an average of two embryos transferred per cycle) was 45% (55/123), 22% (12/54), 54% (75/139), and 48% (40/84) for Groups I-IV, respectively. The clinical pregnancy rate (fetal heart activity per IVF cycle started) was 61% (38/62), 26% (7/27), 69% (49/71), and 71% (30/42), respectively. The live birth rate was 58% (36/62), 22% (6/27), 61% (43/71), and 71% (30/42), respectively, and the live birth per embryo transferred was 40% (49/123), 13% (7/24), 43% (60/139), and 48% (40/84), respectively. There was a significant improvement in implantation, clinical pregnancy, live birth rate and live birth rate per embryo transferred for Group I versus Group II (P = 0.0032, 0.0021, 0.0017, and 0.0002, respectively) and for Group II versus Group IV (P = 0.0021, 0.0002, <0.0001 and <0.0001, respectively). There was no significant difference in success rates between Groups I and III (P = 0.085, 0.23, 0.45, 0.34, respectively) and between Groups III and IV (P = 0.22, 0.48, 0.17, 0.31, respectively)., Conclusion: In subfertile women with preconception Th1:Th2 and/or % CD56(+) cell elevation, IVF success rates are low without IVIG therapy but significantly improve with IVIG therapy. In patients with normal Th1:Th2 and normal CD56(+) cell levels, IVF success rates were not further improved with IVIG therapy. IVIG may be a useful treatment option for patients with previous IVF failure and preconception Th1:Th2 and/or NK elevation. Preconception immune testing may be a critical tool for determining which patients will benefit from IVIG therapy. Prospective controlled studies (preferably double-blind, stratified, and randomized) are needed for confirmation., (© 2011 John Wiley & Sons A/S.)