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In this issue of the Journal, Bushnell and colleagues1 present findings from their analysis of a commercial insurance administrative dataset, examining the ways that antipsychotics are used in young children (aged 2-7 years) in the United States. From 2009 to 2017, they find that the use of antipsychotics decreased and there was a shift toward use of medications in alignment with evidence-based standards. The most common conditions for use of antipsychotics included pervasive developmental disorders, externalizing disorders, and attention-deficit/hyperactivity disorder. More troubling were the findings that less than half of young children on antipsychotics had a visit with a psychiatrist, and only a third of children had evidence of a minimum dose of psychotherapy. These findings deserve attention and should be a cause for strengthening the use of existing treatment guidelines for preschool and younger children. They should also prompt enhanced advocacy to expand access to evidence-based mental health care for children that includes high-quality psychiatric assessment, treatment, and psychotherapy. The latter includes increasing the number of child and adolescent psychiatrists who focus on preschool-aged and younger children.

To describe a direct approach to the deep uterine vein in laparoscopic radical hysterectomy.

Demonstration of the laparoscopic technique with narrated video footage.

Securing sufficient radicality is extremely important when performing a radical hysterectomy for cervical cancer, either by laparotomy or by minimally invasive surgery. The nerve-sparing Okabayashi radical hysterectomy (NS-RH) was originally aimed at achieving both radical resection and function preservation [1-3]. A key procedure when performing NS-RH is intraoperative identification of the relationship between the deep uterine vein and pelvic splanchnic nerve fibers [4]. With this in mind, a safe and easy method for identifying the crossing point of the deep uterine vein and pelvic splanchnic nerve in the initial phase of the surgery may greatly improve the safety and efficacy of functional preservation in NS-RH. Herein, we describe a minimally invasive "direct approach" to the deep uterine vein.

Before undergoing the pelvic lymphadeneco perform the subsequent procedure precisely and securely. This direct approach to the deep uterine vein can be easily and safely performed.

In spring 2020, New York experienced a surge of patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) disease, as part of a global pandemic. There are limited data on populations of COVID-19-infected patients seen by palliative care services.

To describe a palliative care population at one New York hospital system during the initial pandemic surge.

This repeated cross-sectional, observational study collected data on palliative care patients in a large health system seen during the COVID-19 outbreak and compared it with pre-COVID data.

Palliative service volume surged from 678 (4% of total admissions) before COVID-19 to 1071 (10% of total admissions) during the COVID-19 outbreak. During the outbreak, 695 (64.9%) of the total palliative patients tested positive for the virus. Compared with a preoutbreak group, this COVID-19-positive group had higher rates of male (60.7% vs. 48.6%, P<0.01) and Latino (21.3% vs. 13.3%; P<0.01) patients and less white pateline and more acutely ill at the time of admission than pre-COVID-19 palliative patients.

Palliative care triggers have been used in the intensive care unit (ICU) setting, usually in high-income countries, to identify patients who may benefit from palliative care consults. The utility and benefits of palliative care triggers in the ICU have not been previously studied in sub-Saharan Africa.

Our objectives were to determine the prevalence of ICU admissions in those who met at least one palliative care trigger and whether a palliative care consult influenced the length of ICU stay and time to change of goals order.

We conducted a prospective observational cohort study within our ICU at the Aga Khan University Hospital, Nairobi, between December 2019 and August 2020. Data including initiation of a palliative care consult, length of ICU stay, mortality, and time to change of goals order were collected.

During our study period, 72 of 159 (45.9%) patients met at least one palliative care trigger point. Of the patients who met the palliative care triggers, only 29.2% received a palliative care consult. Patients who received palliative care consults had higher rates of change of goals orders signed (52.3%) vs. those who did not (P=0.009). There was no statistically significant difference between the consult and nonconsult groups in regard to length of ICU stay, time to change of goals order, and mortality.

A trigger-based model, geared to the needs of the specific ICU, may be one way of improving integration of palliative care into the ICU, especially in sub-Saharan Africa.

A trigger-based model, geared to the needs of the specific ICU, may be one way of improving integration of palliative care into the ICU, especially in sub-Saharan Africa.

Right ventricular (RV) dysfunction in sepsis and septic shock has been infrequently studied and has uncertain prognostic significance.

Does RV function impact mortality in sepsis and septic shock?

We reviewed the published literature from January 1999 to April 2020 for studies evaluating adult patients with sepsis and septic shock. Study definition of RV dysfunction was used to classify patients. The primary outcome was all-cause mortality divided into short-term mortality (ICU stay, hospital stay, or mortality≤30days) and long-term mortality (>30days). Effect estimates from the individual studies were extracted and combined, using the random-effects, generic inverse variance method of DerSimonian and Laird.

Ten studies, 1,373 patients, were included; RV dysfunction was noted in 477 (34.7%). RV dysfunction was variably classified as decreased RV systolic motion, high RV/left ventricular ratio and decreased RV ejection fraction. Akt inhibitor Septic shock, ARDS, and mechanical ventilation were noted in 82.0%, 27.5%, and 78.4%of the population, respectively. Patients with RV dysfunction had lower rates of mechanical ventilation (71.9%vs81.9%; P< .001), higher rates of acute hemodialysis (38.1%vs22.4%; P= .04), but comparable rates of septic shock and ARDS. Studies showed moderate (I

= 58%) and low (I

= 49%) heterogeneity for short-term and long-term mortality, respectively. RV dysfunction was associated with higher short-term (pooled OR, 2.42; 95%CI, 1.52-3.85; P= .0002) (10 studies) and long-term (pooled OR, 2.26; 95%CI, 1.29-3.95; P= .004) (4 studies) mortality.

In this meta-analysis of observational studies, RV dysfunction was associated with higher short-term and long-term mortality in sepsis and septic shock.

In this meta-analysis of observational studies, RV dysfunction was associated with higher short-term and long-term mortality in sepsis and septic shock.cis-1,2-Dihydro-1,2-naphthalenediol (DHND) is a valuable molecule employed for the pharmaceutical synthesis of bioactive compounds, such as bicyclic conduritol analogues. Enantiopure (+)-(1R,2S)-DHND (>98 % ee) is easily biosynthesized through the dearomatizing dihydroxylation of naphthalene, catalyzed by toluene dioxygenase (TDO) from Pseudomonas putida F1. However, the opposite enantiomer (-)-(1S,2R)-DHND could not be directly accessed, neither by chemical synthesis nor via biocatalytic approaches. Herein, we report a one-step biosynthesis of the opposite enantiomer (-)-(1S,2R)-DHND in a recombinant TDO E. coli BW25113 platform. We based on a semi-rational approach to generate a set of TDO variants, targeting exclusively the hotspot position F366, in order to enable an enantiomeric switch in the generated product. Eight out of nine single point variants were active and showed not only an alteration in enantioselectivity, but also generated an enantiomeric excess of the pursued product. Variant TDOF366V outperformed above the rest of the set, enabling the synthesis of (-)-(1S,2R)-DHND not only with an excellent enantiomeric excess of 90 %, but also with an advantageous product formation. A comparative semi-preparative biosynthesis yielded, 287 mg of (+)-(1R,2S)-DHND (>98 % ee) and 101 mg of (-)-(1S,2R)-DHND (90 % ee), when performed in a total volume of 100 mL with TDO wild-type and TDOF366V resting cells, respectively.Obtaining large-scale hairy root cultures is a major challenge to increasing root biomass and secondary metabolite production. Enhanced production of stilbene compounds such as trans-resveratrol, trans-arachidin-1 and trans-arachidin-3 was achieved using an elicitor treatment procedure. Two different hairy root inoculum densities were investigated and compared between shake flask and bioreactor cultures. The lowest growth index was observed using a 20 g/L inoculum size in the bioreactor, which differed significantly from bioreactor of 5 g/L. Increasing the hairy root inoculum size from 5 g/L to 20 g/L in both the shake flask and bioreactor significantly improve antioxidant activity, phenolic content and stilbene compound levels. The highest ABTS and FRAP antioxidant activity, and levels of total phenolic compounds, trans-arachidin-1 and trans-arachidin-3 in the crude extract were demonstrated in shake flask cultures with a 20 g/L inoculum after elicitation for 72 h. The minimum inhibitory concentrations (MICs) of the crude extract to inhibit growth of foodborne microbes, S. aureus, S. typhimurium and E. coli, were 187.5, 250 and 500 μg/mL, respectively. This was due to the ability of the crude extract to disrupt the cell membrane, as observed by scanning electron microscopy (SEM) showing ruptured pores on the S. aureus and S. typhimurium cell surfaces. Moreover, the E. coli cell division process could be inhibited by the crude extract, which promoted an increase in cell size. A DNA nicking assay indicated that a 50 μg/mL concentration of the crude extract caused plasmid DNA damage that might be due to a genotoxic effect of the pro-oxidant activity of the crude extract.The optimal conditions for high biomass and lipid production from Nannochloris atomus were evaluated. The parameters used in this study were light emitting diode (LED) wavelength mixing ratio, the photoperiod, salinity tolerance, and single and combined stresses. Biomass production was monitored in the first phase using red LED (625 nm), followed by lipid production by green LED (520 nm) in the second phase. The optimal conditions were obtained using a single red LED with lightdark durations of 204 h and two days of exposure in combined stresses of 1.06 M NaCl and green LED. Under these conditions, 68.6 % (w/w) lipid content were obtained. Compared to the non-stress control, the lipid content was increased by 31.9 %. Linolenic acid (C183) the omega-3 fatty acid was produced up to 52.4 % in 1.06 M NaCl as a single stress.Osteosarcoma (OS) is the most common primary malignancy of the bone and has a high propensity for local invasion and metastasis. Although combining surgery with chemotherapy has immensely improved the outcomes of osteosarcoma patients, the prognosis of metastatic or recurrent osteosarcomas is still unsatisfactory. Immunotherapy has proven to be a promising therapeutic strategy against human malignancies and improved understanding of the immune response to OS, and biomarker development has increased the number of patients who benefit from immunotherapies in recent years. Here, we review recent advances in immunotherapy in osteosarcoma and discuss the mechanisms and status of immunotherapies in both preclinical and clinical trials as well as future therapies on the horizon. These advances may pave the way for novel treatments requisite for patients with osteosarcoma in need of new therapies.